Cellular signalling by primary cilia in development, organ function and disease

In the paper

“whereas the IFT-B complex proteins IFT25 and IFT27 are involved in ciliary export of hedgehog (HH) signalling components via retrograde IFT 59, 60, 62, 63.”

What the sources say

• Disputed

  The Introduction (page unavailable) assigns anterograde trafficking to IFT-B and retrograde trafficking to IFT-A, contrary to the cited sentence’s assignment of retrograde export to IFT-B proteins. Our copy does not identify IFT25 or IFT27 or establish a specific exception for them. (LLM, conf=0.76)

  Checked by a reasoning model — may be wrong.

  cites [59] Liem, K. F. Jr. et al. The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking. J. Cell Biol. 197, 789–800 (2012). sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction and Discussion report that IFT25 is required for ciliary export of the Hedgehog components Ptch1 and Smo. The Results show that IFT27 is depleted from cilia lacking IFT25, but the Discussion says IFT27’s contribution remains unclear. The paper presents export through IFT as a model, rather than directly establishing that both proteins mediate it via retrograde IFT. Page numbers were not available in our copy. (LLM, conf=0.86)

  cites [60] Keady, B. T. et al. IFT25 links the signal-dependent movement of Hedgehog components to intraflagellar transport. Dev. Cell 22, 940–951 (2012). sourceExperimental — accuracy not yet measured
• ?Could not verify

  Our copy’s Abstract discusses IFT74 and IFT81 binding tubulin and their role in ciliogenesis, not IFT25 or IFT27. Searches for IFT25/IFT27 and hedgehog-component export via retrograde IFT found no passage addressing the claim; page numbers are unavailable in the copy. (LLM, conf=0.76)

  cites [62] Bhogaraju, S. et al. Molecular basis of tubulin transport within the cilium by IFT74 and IFT81. Science 341, 1009–1012 (2013). sourceExperimental — accuracy not yet measured

In the paper

“A report of the near-atomic-resolution structure of the human PC1-PC2 complex by single-particle cryo-electron microscopy, however, strongly favours a model in which PC1 and PC2 function together in regulating cation transport 94.”

What the sources say

• Disputed

  The Introduction describes a cryo-EM structure of PC2 alone as a homotetramer, not a near-atomic-resolution structure of a human PC1–PC2 complex. The Discussion section on loss of PC1 reports that PC1 is not essential for basal PC2 ciliary currents, contrary to the claim that this paper's structural evidence strongly favours their functioning together in cation transport. The authors do not exclude a possible association between them. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  cites [94] Liu, X. et al. Polycystin-2 is an essential ion channel subunit in the primary cilium of the renal collecting duct epithelium. eLife 7, e33183 (2018). sourceExperimental — accuracy not yet measured

In the paper

“Emerging evidence indicates that the constellation of signalling components within the cilium is also dynamic and closely coupled to the differentiation state and microenvironment of the cell 3.”

What the sources say

• Partly supported

  The Concluding remarks describe the cilium as a dynamic organelle whose proteins interact in changing functional networks. “Unique spatiotemporal roles of ciliary proteins” links ciliation and Hedgehog signalling to differentiation and describes cilia restricted to particular extracellular-matrix zones. These passages do not establish that the specific set of signalling components within a cilium changes in close response to both differentiation state and microenvironment. (LLM, conf=0.82)

  cites [3] Heydeck, W., Fievet, L., Davis, E. E. & Katsanis, N. The complexity of the cilium: spatiotemporal diversity of an ancient organelle. Curr. Opin. Cell Biol. 55, 139–149 (2018). sourceExperimental — accuracy not yet measured

In the paper

“For example, transition fibres mediate docking of the basal body to the plasma membrane or vesicles during early stages of ciliogenesis 4, 5”

What the sources say

• Partly supported

  The early-formation account (p. 365) says a primary ciliary vesicle attaches to the distal end of the centriole. The discussion (p. 374) also describes centriole attachment to the plasma membrane in another cell type, but questions whether attachment to the cell surface is obligatory. The paper does not identify transition fibres as mediating either attachment; it suggests that centriolar arms may help stabilize the centriole during cilium emergence. (LLM, conf=0.84)

  cites [4] Sorokin, S. Centrioles and the formation of rudimentary cilia by fibroblasts and smooth muscle cells. J. Cell Biol. 15, 363–377 (1962). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [5] Sorokin, S. P. Reconstructions of centriole formation and ciliogenesis in mammalian lungs. J. Cell Sci. 3, 207–230 (1968). source

In the paper

“For example, flagella in a Chlamydomonas bbs4 mutant show abnormal accumulation of several signalling proteins, resulting in disrupted phototaxis 72.”

What the sources say

• Partly supported

  The Introduction reports abnormal accumulation of several likely signaling proteins in BBS-mutant flagella and loss of phototaxis. The section on newly assembled bbs4-1 flagella reports transiently improved phototaxis, but says the accumulation *suggests* an impairment; the claim presents that proposed causal link as established. (LLM, conf=0.85)

  cites [72] Lechtreck, K. F. et al. The Chlamydomonas reinhardtii BBSome is an IFT cargo required for export of specific signaling proteins from flagella. J. Cell Biol. 187, 1117–1132 (2009). sourceExperimental — accuracy not yet measured

In the paper

“In addition, a complex of BBS proteins called the BBSome 70, was shown to function as an IFT adapter 71, 72 in transporting ciliary proteins.”

What the sources say

• ?Could not verify

  The introduction (p. 1) describes IFT complexes A and B, and the Discussion (p. 7) discusses IFT-A and Tulp3 in ciliary trafficking. Neither passage identifies the BBSome or says it functions as an IFT adapter; searches for “BBSome” and “Bardet-Biedl proteins adapter” found no such passage in our copy. (LLM, conf=0.75)

  cites [70] Boubakri, M. et al. Loss of ift122, a retrograde intraflagellar transport (IFT) complex component, leads to slow, progressive photoreceptor degeneration due to inefficient opsin transport. J. Biol. Chem. 291, 24465–24474 (2016). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [71] Nachury, M. V. et al. A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell 129, 1201–1213 (2007). source
• Partly supported

  The Introduction identifies the BBSome as a complex of BBS proteins and concludes that it is carried by IFT as an adapter. It proposes a role in exporting certain proteins from Chlamydomonas flagella, but says BBS4 may be required for that export. Thus, saying the BBSome was shown to transport ciliary proteins states the proposed cargo-transport role more definitively and broadly than the source does. (LLM, conf=0.86)

  cites [72] Lechtreck, K. F. et al. The Chlamydomonas reinhardtii BBSome is an IFT cargo required for export of specific signaling proteins from flagella. J. Cell Biol. 187, 1117–1132 (2009). sourceExperimental — accuracy not yet measured

In the paper

“and the intraflagellar transport (IFT) system that zips up and down axonemal microtubules to mediate the transport of specific ciliary cargo proteins into or out of the organelle 24, 25 (Figure 1).”

What the sources say

• Supported

  The section “IFT: the protein translocation machinery of cilia” states that IFT trains move bidirectionally on axonemal microtubules and carry other proteins as cargo. The Abstract also states that IFT imports and exports proteins in cilia. The supplied passages have section labels but no page numbers. (LLM, conf=0.94)

  cites [24] Lechtreck, K. F. IFT-cargo interactions and protein transport in cilia. Trends Biochem. Sci. 40, 765–778 (2015). source
• Supported

  The paper’s Abstract says anterograde and retrograde IFT trains run on the tubules of axonemal microtubule doublets. Its description of the IFT cycle says trains carry ciliary cargo from the base to the tip and carry cargo or turnover products back toward the base. Page numbers are not available in our copy. (LLM, conf=0.93)

  cites [25] Taschner, M. & Lorentzen, E. The intraflagellar transport machinery. Cold Spring Harb. Perspect. Biol. 8, a028092 (2016). source

In the paper

“Purification of the polypeptides within the particles moved by IFT 44, demonstrated that they sediment as two larger complexes, termed IFT-A and IFT-B 44, 45.”

What the sources say

• Supported

  The Results section, “Hydrodynamic Analysis of the IFT Particle Polypeptides,” reports that the 15 polypeptides could be separated into two sedimenting complexes, A and B. The Discussion section, “IFT Particles Are Composed of Two Large Protein Complexes,” identifies them as large complexes of 550 and 710–760 kD. (LLM, conf=0.94)

  cites [44] Cole, D. G. et al. Chlamydomonas kinesin-II-dependent intraflagellar transport (IFT): IFT particles contain proteins required for ciliary assembly in Caenorhabditis elegans sensory neurons. J. Cell Biol. 141, 993–1008 (1998). source
• Partly supported

  The Results (page not provided) report isolating and sedimenting a complex of at least 13 flagellar polypeptides, which supports the purification and sedimentation part of the claim. They identify one 17S complex, not two complexes termed IFT-A and IFT-B; the separate 11S peak contains inner dynein arm components. (LLM, conf=0.88)

  cites [45] Piperno, G. & Mead, K. Transport of a novel complex in the cytoplasmic matrix of Chlamydomonas flagella. Proc. Natl Acad. Sci. USA 94, 4457–4462 (1997). sourceExperimental — accuracy not yet measured

In the paper

“For example, metazoans such as Caenorhabditis elegans and zebrafish express a homodimeric kinesin-2 motor that functions somewhat redundantly with heterotrimeric kinesin-2 to mediate anterograde IFT and distal singlet axonemal microtubule assembly in certain types of cilia 40–43.”

What the sources say

• ?Not checked — no full text of the sourcecites [40] Ou, G., Blacque, O. E., Snow, J. J., Leroux, M. R. & Scholey, J. M. Functional coordination of intraflagellar transport motors. Nature 436, 583–587 (2005). source
• Partly supported

  The paper identifies homodimeric OSM-3 and heterotrimeric kinesin-II in C. elegans sensory cilia (p. 3) and reports that they act redundantly in anterograde IFT along the middle segment (p. 6). It does not address zebrafish. It also says OSM-3 acts alone in distal-segment IFT and is essential for distal-segment assembly (pp. 6–7), so redundancy does not extend to that assembly. (LLM, conf=0.88)

  cites [41] Snow, J. J. et al. Two anterograde intraflagellar transport motors cooperate to build sensory cilia on C. elegans neurons. Nat. Cell Biol. 6, 1109–1113 (2004). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [42] Zhao, C., Omori, Y., Brodowska, K., Kovach, P. & Malicki, J. Kinesin-2 family in vertebrate ciliogenesis. Proc. Natl Acad. Sci. USA 109, 2388–2393 (2012). source
• ?Not checked — no full text of the sourcecites [43] Prevo, B., Mangeol, P., Oswald, F., Scholey, J. M. & Peterman, E. J. Functional differentiation of cooperating kinesin-2 motors orchestrates cargo import and transport in C. elegans cilia. Nat. Cell Biol. 17, 1536–1545 (2015). source

In the paper

“Furthermore, the IFT-A complex interacts with the tubby domain proteins TULP3 and TUB to mediate ciliary targeting of certain transmembrane proteins, including G protein-coupled receptors (GPCRs) 56, 58, 64–69.”

What the sources say

• ?Not checked — no full text of the sourcecites [56] Qin, H. et al. Intraflagellar transport is required for the vectorial movement of TRPV channels in the ciliary membrane. Curr. Biol. 15, 1695–1699 (2005). source
• ?Not checked — no full text of the sourcecites [58] Behal, R. H. et al. Subunit interactions and organization of the Chlamydomonas reinhardtii intraflagellar transport complex A proteins. J. Biol. Chem. 287, 11689–11703 (2012). source
• ?Not checked — no full text of the sourcecites [64] Mourão, A., Christensen, S. T. & Lorentzen, E. The intraflagellar transport machinery in ciliary signaling. Curr. Opin. Struct. Biol. 41, 98–108 (2016). source
• Supported

  The Introduction states that TULP3 and TUB bind the IFT-A core complex and describes their roles in trafficking GPCRs to cilia. The “Differential effects of Tulp3 and Tub on ciliary GPCR trafficking” section also reports IFT-A binding by TUB and its role in GPCR trafficking; the conclusion extends the mechanism to diverse integral membrane proteins. Page numbers are not provided in our copy. (LLM, conf=0.94)

  cites [65] Badgandi, H. B., Hwang, S. H., Shimada, I. S., Loriot, E. & Mukhopadhyay, S. Tubby family proteins are adapters for ciliary trafficking of integral membrane proteins. J. Cell Biol. 216, 743–760 (2017). source
• Partly supported

  The Introduction states that the IFT-A core is associated with TULP3, and the Results report impaired ciliary entry of the GPCR SMO in cells lacking an IFT-A subunit. However, the paper does not describe an interaction with TUB or establish that TULP3 and TUB mediate GPCR targeting through IFT-A. (LLM, conf=0.85)

  cites [66] Takahara, M. et al. Ciliopathy-associated mutations of IFT122 impair ciliary protein trafficking but not ciliogenesis. Hum. Mol. Genet. 27, 516–528 (2018). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (page unavailable) show that TULP3 interacts with the IFT-A core, and that a functional IFT-A complex is required for ciliary entry of several GPCRs. The paper does not establish an interaction between IFT-A and TUB, so it supports the TULP3 and GPCR portions of the claim but not the named role of TUB. (LLM, conf=0.88)

  cites [67] Hirano, T., Katoh, Y. & Nakayama, K. Intraflagellar transport-A complex mediates ciliary entry and retrograde trafficking of ciliary G protein-coupled receptors. Mol. Biol. Cell 28, 429–439 (2017). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section, “Integrated function of Wdr35-IFT-A complex” (page unavailable), reports interactions between IFT-A subunits and ciliary membrane cargoes, including the GPCR SSTR3, supporting a role in cargo transport. Our copy does not report interactions with TULP3 or TUB; TULP3 appears in the title of a work listed in the References, but that does not establish the claimed interactions for this paper. (LLM, conf=0.86)

  cites [68] Fu, W., Wang, L., Kim, S., Li, J. & Dynlacht, B. D. Role for the IFT-A complex in selective transport to the primary cilium. Cell Rep. 17, 1505–1517 (2016). sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion (p. 9) says IFT-A helps translocate membrane proteins, including SMO, into cilia, and the results (p. 5) show that ciliary entry of EVC, EVC2 and SMO requires an IFT-A subunit. Our copy does not say that IFT-A interacts with TULP3 or the tubby-domain protein TUB, or that such an interaction mediates this targeting. (LLM, conf=0.85)

  cites [69] Caparrós-Martín, J. A. et al. Specific variants in WDR35 cause a distinctive form of Ellis-van Creveld syndrome by disrupting the recruitment of the EvC complex and SMO into the cilium. Hum. Mol. Genet. 24, 4126–4137 (2015). sourceExperimental — accuracy not yet measured

In the paper

“Importantly, a number of genes mutated in ciliopathies such as Joubert syndrome, Meckel-Gruber syndrome (MKS), and nephronophthisis (NPHP), encode protein module components of the TZ or basal body transition fibres, highlighting the physiological importance of these structures 21.”

What the sources say

• Supported

  The Transition Zone Architecture section links the NPHP transition-zone complex to nephronophthisis and the MKS complex to Meckel-Gruber and Joubert syndromes. The Ciliary Gate Diseases section also describes a table identifying disease-associated genes and their locations, including transition fibers. Together these passages support the claim that mutations affecting these structures are associated with ciliopathies. (LLM, conf=0.90)

  cites [21] Garcia-Gonzalo, F. R. & Reiter, J. F. Open sesame: how transition fibers and the transition zone control ciliary composition. Cold Spring Harb. Perspect. Biol. 9, a028134 (2016). source

In the paper

“These include vesicular transport pathways that target specific receptors or signalling molecules from the Golgi or recycling endosome to the ciliary base where vesicles are exocytosed 22, 23,”

What the sources say

• Partly supported

  The ‘Vesicular and membrane trafficking for ciliary proteins’ section describes possible routes from the trans-Golgi network to the periciliary membrane, including one via the recycling endosome. ‘Trafficking directly to the periciliary membrane’ says vesicle fusion there is probable, not established; the citing sentence presents that step as definite. Page numbers are unavailable in our copy. (LLM, conf=0.82)

  cites [22] Sung, C. H. & Leroux, M. R. The roles of evolutionarily conserved functional modules in cilia-related trafficking. Nat. Cell Biol. 15, 1387–1397 (2013). sourceExperimental — accuracy not yet measured
• Supported

  The Assembly of primary cilia section describes vesicular transport of ciliary membrane proteins from the trans-Golgi network or recycling endosome to the ciliary base, followed by vesicle fusion. The Structure of primary cilia section identifies the membrane around the ciliary base as a site of vesicle exocytosis. The claim is a supported paraphrase of those passages. (LLM, conf=0.93)

  cites [23] Morthorst, S. K., Christensen, S. T. & Pedersen, L. B. Regulation of ciliary membrane protein trafficking and signalling by kinesin motor proteins. FEBS J. 285, 4535–4564 (2018). source

In the paper

“Moreover, ciliary membrane content can be modulated by the ectocytosis of vesicles at the ciliary tip 26–28 (Figure 1).”

What the sources say

• Partly supported

  The Results section on ciliary ectosomes reports vesicles budding from Chlamydomonas flagellar membranes, and the Discussion identifies flagellar membrane proteins in the released vesicles. This supports ectocytosis as a way to remove ciliary membrane content, but the copy does not establish that the vesicles bud specifically at the ciliary tip; the immunofluorescence Results report only that the cargo protein often clusters toward the distal end. Page numbers were not provided. (LLM, conf=0.85)

  cites [26] Wood, C. R., Huang, K., Diener, D. R. & Rosenbaum, J. L. The cilium secretes bioactive ectosomes. Curr. Biol. 23, 906–911 (2013). sourceExperimental — accuracy not yet measured
• Supported

  The Results section on ciliary receptor interactions reports signaling-induced shedding of ciliary membrane vesicles, many observed near the tips. The Discussion explains that this shedding moves a ciliary membrane protein into the extracellular milieu, supporting modulation of ciliary membrane content. (LLM, conf=0.91)

  cites [27] Cao, M. et al. Uni-directional ciliary membrane protein trafficking by a cytoplasmic retrograde IFT motor and ciliary ectosome shedding. eLife 4, e05242 (2015). sourceExperimental — accuracy not yet measured
• Supported

  The Introduction describes activated receptors concentrating at ciliary tips and leaving in ectosomes. The Results report that ectocytosis removes enough ciliary material to reduce cilium length, supporting the claim that tip vesicle release can change ciliary membrane content. (LLM, conf=0.94)

  cites [28] Nager, A. R. et al. An actin network dispatches ciliary GPCRs into extracellular vesicles to modulate signaling. Cell 168, 252–263 (2017). sourceExperimental — accuracy not yet measured

In the paper

“For instance, the IFT-B complex proteins IFT-81 and IFT-74 promote anterograde IFT of tubulin towards the ciliary tip during axoneme assembly 61,”

What the sources say

• Partly supported

  The Introduction says IFT-B helps transport components into cilia for assembly, and the References list a study of tubulin transport by IFT74 and IFT81. The cited paper does not state that these proteins promote anterograde tubulin transport to the ciliary tip during axoneme assembly; its discussion of IFT81/IFT74 concerns their possible interaction with IFT25/IFT27. (LLM, conf=0.78)

  cites [61] Eguether, T. et al. IFT27 links the BBSome to IFT for maintenance of the ciliary signaling compartment. Dev. Cell 31, 279–290 (2014). sourceExperimental — accuracy not yet measured

In the paper

“A few years later, studies using temperature sensitive C. reinhardtii mutants with defects in flagellar assembly revealed that anterograde and retrograde IFT movements are powered by heterotrimeric kinesin-2 33–35 and cytoplasmic dynein 2 motors 36–38, respectively.”

What the sources say

• Partly supported

  In the discussion of KHP1 and flagellar assembly (around pp. 185–186), the paper studies temperature-sensitive fla10 mutants and proposes that their kinesin-like protein may transport components toward flagellar tips. It presents that transport role as a model, not a demonstration that heterotrimeric kinesin-2 powers anterograde IFT. The citation is attached to the kinesin-2 portion of the citing sentence; the separately cited dynein-2 portion is not attributed to this paper. (LLM, conf=0.88)

  cites [33] Walther, Z., Vashishtha, M. & Hall, J. L. The Chlamydomonas FLA10 gene encodes a novel kinesin-homologous protein. J. Cell Biol. 126, 175–188 (1994). sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion (pp. 1524–1525) reports that IFT stopped in a temperature-sensitive FLA10 mutant and proposes FLA10 as a motor for movement toward the flagellar tip. It does not establish that FLA10 directly powers anterograde IFT or that it forms a heterotrimeric kinesin-2 complex; the latter is discussed by analogy with homologues. The separate citations attached to the dynein-2 claim are not assessed here. (LLM, conf=0.88)

  cites [34] Kozminski, K. G., Beech, P. L. & Rosenbaum, J. L. The Chlamydomonas kinesin-like protein FLA10 is involved in motility associated with the flagellar membrane. J. Cell Biol. 131, 1517–1527 (1995). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [35] Vashishtha, M., Walther, Z. & Hall, J. L. The kinesin-homologous protein encoded by the Chlamydomonas FLA10 gene is associated with basal bodies and centrioles. J. Cell Sci. 109, 541–549 (1996). source
• Partly supported

  The Results section, “Retrograde IFT Is Defective in LC8 Mutants,” reports that fla14 mutants almost completely lack retrograde IFT while anterograde IFT appears normal. But the Discussion, “Cytoplasmic Dynein Is Likely To Be the Motor for Retrograde IFT,” calls dynein the most likely motor, says the motor is not yet known, and does not rule out a minus-end-directed kinesin. This paper’s fla14 mutants are LC8-gene deletion mutants, not the temperature-sensitive fla10 mutants discussed for anterograde IFT. (LLM, conf=0.89)

  cites [36] Pazour, G. J., Wilkerson, C. G. & Witman, G. B. A dynein light chain is essential for retrograde particle movement in intraflagellar transport (IFT). J. Cell Biol. 141, 979–992 (1998). sourceExperimental — accuracy not yet measured
• Partly supported

  The Abstract and Discussion (page unavailable in our copy) identify DHC1b as a cytoplasmic dynein and conclude that it is probably the motor for retrograde IFT. But this paper studied a deletion mutant, not a temperature-sensitive mutant, and it inferred the motor's role rather than directly demonstrating retrograde movement in that mutant. The anterograde kinesin finding is reported as background and is covered by separate citations in the citing sentence. (LLM, conf=0.88)

  cites [37] Pazour, G. J., Dickert, B. L. & Witman, G. B. The DHC1b (DHC2) isoform of cytoplasmic dynein is required for flagellar assembly. J. Cell Biol. 144, 473–481 (1999). sourceExperimental — accuracy not yet measured
• Partly supported

  In the Discussion (page unavailable), the paper reports flagellar-assembly defects in Chlamydomonas mutants with deletions in the cytoplasmic dynein 1b gene. It says dynein 1b *could* serve as the retrograde IFT motor, rather than showing that it powers retrograde movement. The mutants studied were generated by insertional mutagenesis, not identified as temperature-sensitive mutants. (LLM, conf=0.88)

  cites [38] Porter, M. E., Bower, R., Knott, J. A., Byrd, P. & Dentler, W. Cytoplasmic dynein heavy chain 1b is required for flagellar assembly in Chlamydomonas. Mol. Biol. Cell 10, 693–712 (1999). sourceExperimental — accuracy not yet measured

In the paper

“Sequence analysis of IFT polypeptides isolated from C. reinhardtii flagella revealed that they are homologous to proteins required for ciliary assembly in sensory neurons of C. elegans 44, 53, providing the first evidence that IFT is an evolutionarily conserved process required for ciliary assembly in eukaryotes.”

What the sources say

• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [44] Cole, D. G. et al. Chlamydomonas kinesin-II-dependent intraflagellar transport (IFT): IFT particles contain proteins required for ciliary assembly in Caenorhabditis elegans sensory neurons. J. Cell Biol. 141, 993–1008 (1998). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [53] Jordan, M. A., Diener, D. R., Stepanek, L. & Pigino, G. The cryo-EM structure of intraflagellar transport trains reveals how dynein is inactivated to ensure unidirectional anterograde movement in cilia. Nat. Cell Biol. 20, 1250–1255 (2018). source

In the paper

“Binding of cholesterol to the extracellular cysteine rich domain of SMO dramatically changes the conformation of this domain with respect to the transmembrane domains, leading to release of the π-cation lock.”

What the sources say

• ?Could not verify

  The paper’s structural discussion (page unavailable) concerns Patched-1 and its complex with Sonic Hedgehog, not a cholesterol-bound SMO structure. Searches for SMO’s cysteine-rich domain, its movement relative to the transmembrane domains, and a π-cation lock found no passage addressing the claimed mechanism. (LLM, conf=0.76)

  cites [113] Qi, X., Schmiege, P., Coutavas, E., Wang, J. & Li, X. Structures of human Patched and its complex with native palmitoylated sonic hedgehog. Nature 560, 128–132 (2018). sourceExperimental — accuracy not yet measured

In the paper

“The above-described studies of IFT in Chlamydomonas set the stage for a landmark study which revealed that a hypomorphic mutation in the mouse Tg737 gene, which encodes an orthologue of the Chlamydomonas IFT-B polypeptide IFT88, causes ciliary loss and autosomal recessive (AR) PKD 79, 80.”

What the sources say

• Partly supported

  The Results section identifies Tg737 and IFT88 as likely orthologs and reports that hypomorphic Tg737-mutant mice have kidney disease. But the kidney-cilia Results section says the mutants retain numerous cilia that are much shorter than normal, not that they lose cilia. The Discussion says their disease closely resembles human autosomal recessive polycystic kidney disease, rather than identifying it as the human disease. (LLM, conf=0.90)

  cites [79] Pazour, G. J. et al. Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J. Cell Biol. 151, 709–718 (2000). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [80] Moyer, J. et al. Candidate gene associated with a mutation causing recessive polycystic kidney disease in mice. Science 264, 1329–1333 (1994). source

In the paper

“However, the solved structures of PTCH1 bound or unbound to SHH 111, 112 and SMO bound or unbound to cholesterol derivatives 113 reveal important insights.”

What the sources say

• ?Could not verify

  Citation 113 is attached to the SMO structures, not the PTCH1 structures. The Results section, “Smoothened can couple to Gi proteins outside primary cilia” (page unavailable), reports a signaling experiment; searches for SMO structures and cholesterol derivatives found no passage in our copy addressing the claimed structural insights. (LLM, conf=0.76)

  cites [111] Ho Wei, L., Arastoo, M., Georgiou, I., Manning, D. R. & Riobo-Del Galdo, N. A. Activation of the Gi protein-RHOA axis by non-canonical Hedgehog signaling is independent of primary cilia. PLOS ONE 13, e0203170 (2018). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [112] Gong, X. et al. Structural basis for the recognition of Sonic Hedgehog by human Patched1. Science 361, eaas8935 (2018). source
• Supported

  The paper’s Abstract reports cryo-EM structures of human Patched-1 alone and in complex with Sonic Hedgehog, matching the PTCH1 portion of the citing sentence. The separate claim about SMO structures is attributed to citation 113, not this paper. (LLM, conf=0.93)

  cites [113] Qi, X., Schmiege, P., Coutavas, E., Wang, J. & Li, X. Structures of human Patched and its complex with native palmitoylated sonic hedgehog. Nature 560, 128–132 (2018). source

In the paper

“In the absence of SHH, PKA-mediated phosphorylation of GLI3 primes sequential phosphorylation events by casein kinase 1 (CK1) and glycogen synthase kinase-3 beta (GSK3β), which results in binding of GLI3 to the SCFβTrCP ubiquitin ligase, and its subsequent proteolysis into GLI3R 118–121.”

What the sources say

• Supported

  The paper’s introductory pathway description says that, in the absence of Hh, PKA primes Gli2/Gli3 phosphorylation by GSK3β and CK1, recruiting βTrCP and SCF1 and leading to proteasomal cleavage into repressors. The Results section (“Gpr175 Inhibits Gli3 Processing”) likewise states that PKA initiates the cascade that produces Gli3-R. (LLM, conf=0.90)

  cites [118] Singh, J., Wen, X. & Scales, S. J. The orphan G protein-coupled receptor Gpr175 (Tpra40) enhances Hedgehog signaling by modulating cAMP levels. J. Biol. Chem. 290, 29663–29675 (2015). source
• Partly supported

  The Introduction (page unavailable) states that, in the absence of Shh, full-length Gli3 is proteolytically processed into the repressor Gli3R. Our copy does not describe the claimed PKA, CK1 and GSK3β phosphorylation sequence or binding to SCFβTrCP; a search for those terms found no supporting passage. (LLM, conf=0.88)

  cites [119] Haycraft, C. J. et al. Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLOS Genet. 1, e53 (2005). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [120] Jiang, J. & Struhl, G. Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb. Nature 391, 493–496 (1998). source
• ?Not checked — no full text of the sourcecites [121] Tempe, D., Casas, M., Karaz, S., Blanchet-Tournier, M. F. & Concordet, J. P. Multisite protein kinase A and glycogen synthase kinase 3beta phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP. Mol. Cell. Biol. 26, 4316–4326 (2006). source

In the paper

“This study provided the first evidence that defective primary cilia can lead to disease in mammals, and was supported by prior work in C. elegans demonstrating that homologs of the human autosomal dominant (AD) PKD1 and PKD2 gene products, the transmembrane proteins polycystin (PC) 1 and PC2, localize to neuronal sensory cilia and regulate male mating behaviour 81.”

What the sources say

• Supported

  The Results section reports that kidney primary cilia are markedly shorter in Tg737-mutant mice. The Discussion links the same mutation to cystic kidney disease and describes the findings as new evidence connecting defective ciliary assembly with disease in mice. The claim says the study provided evidence, not that it proved ciliary defects alone cause the disease. (LLM, conf=0.85)

  cites [79] Pazour, G. J. et al. Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J. Cell Biol. 151, 709–718 (2000). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [80] Moyer, J. et al. Candidate gene associated with a mutation causing recessive polycystic kidney disease in mice. Science 264, 1329–1333 (1994). source

In the paper

“The physiological importance of the polycystins is underscored by the fact that mutations in the corresponding genes lead to ADPKD — a disease characterized by the adult-onset development of kidney and liver cysts 85, 86.”

What the sources say

• Partly supported

  The paper’s Abstract identifies PKD1 and PKD2 as the genes encoding PC1 and PC2 and says that ADPKD commonly involves kidney and liver cysts. It says kidney cysts typically become clinically apparent by the fourth decade, not that kidney and liver cysts both begin developing in adulthood; it also notes that kidney cysts can be present early in life. The adult-onset development qualifier is therefore not supported as stated. (LLM, conf=0.86)

  cites [85] Ma, M., Gallagher, A. R. & Somlo, S. Ciliary mechanisms of cyst formation in polycystic kidney disease. Cold Spring Harb. Perspect. Biol. 9, a028209 (2017). sourceExperimental — accuracy not yet measured
• Partly supported

  The section “Detecting flow in the node: the three hypotheses” (page unavailable) identifies Pkd1 and Pkd2 as polycystic kidney disease genes and discusses their proteins’ function in the kidney. It does not state that mutations in those genes cause autosomal dominant polycystic kidney disease or describe adult-onset kidney and liver cysts. (LLM, conf=0.76)

  cites [86] Norris, D. P. Cilia, calcium and the basis of left-right asymmetry. BMC Biol. 10, 102 (2012). sourceExperimental — accuracy not yet measured

In the paper

“In contrast, basal repression in the absence of SHH involves protein kinase A (PKA)-mediated phosphorylation, predominantly of GLI3, and formation of the truncated N-terminal form of GLI, GLIR, in a cilia-dependent manner 104.”

What the sources say

• Partly supported

  The Introduction says that when Hedgehog signaling is off, Gli2/3 become truncated repressors; the Results identify Gli3 as the major repressor in most tissues and show PKA-dependent truncation of Gli3 in unstimulated cells. The Introduction discusses ciliary Smoothened inhibiting repressor formation after Hedgehog stimulation, but the passages do not establish that basal repressor formation itself is cilia-dependent. Page numbers are unavailable in our copy. (LLM, conf=0.84)

  cites [104] Niewiadomski, P. et al. Gli protein activity is controlled by multisite phosphorylation in vertebrate Hedgehog signaling. Cell Rep. 6, 168–181 (2014). sourceExperimental — accuracy not yet measured

In the paper

“and HH-stimulated chemotaxis is mediated by SMO localized outside of cilia 109.”

What the sources say

• Partly supported

  The Results section reports that, when IFT80 deletion caused cilia loss, SMO became cytoplasmic and Hedgehog stimulation favored non-canonical signaling. The paper does not show that this SMO localization mediates chemotaxis; its Discussion describes chemotaxis as a finding reported by other studies (pages unavailable in our copy). (LLM, conf=0.84)

  cites [109] Yuan, X. et al. Ciliary IFT80 balances canonical versus non-canonical hedgehog signalling for osteoblast differentiation. Nat. Commun. 7, 11024–11024 (2016). sourceExperimental — accuracy not yet measured

In the paper

“Downstream factors that mediate SMO-dependent activation of GLI2 are varied, and include G proteins and other proteins such as the EVC2 complex 104, 115.”

What the sources say

• Partly supported

  The Introduction (page unavailable) describes Smoothened as controlling Gli activator production, and the Results section on Gli2 transcriptional activity shows that Smoothened signaling regulates Gli2. But the paper does not identify G proteins or the EVC2 complex as downstream mediators; searches for EVC2 and G proteins found no supporting passage. (LLM, conf=0.86)

  cites [104] Niewiadomski, P. et al. Gli protein activity is controlled by multisite phosphorylation in vertebrate Hedgehog signaling. Cell Rep. 6, 168–181 (2014). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Abstract says Smo activity allows Gli transcription factors to initiate target-gene transcription, but it does not identify mediators of GLI2 activation. The Discussion says that coupling to distinct downstream signaling complexes remains to be determined. Searches for EVC2 and G proteins as downstream mediators found no passage supporting the attributed examples. (LLM, conf=0.72)

  cites [115] Nachtergaele, S. et al. Oxysterols are allosteric activators of the oncoprotein Smoothened. Nat. Chem. Biol. 8, 211–220 (2012). sourceExperimental — accuracy not yet measured

In the paper

“For example, the IFT-B complex protein, IFT80, can repress SHH-mediated noncanonical activation of the GTPase RHOA in differentiating mouse osteoblasts 108,”

What the sources say

• Partly supported

  The Hedgehog signal transduction section describes a transcription-independent Shh response, supporting the general reference to noncanonical signaling. It does not identify IFT80, RHOA, or differentiating mouse osteoblasts, so it does not support the specific repression mechanism claimed. Page numbers are unavailable in our copy. (LLM, conf=0.81)

  cites [108] Bijlsma, M. F. & Roelink, H. Non-cell-autonomous signaling by Shh in tumors: challenges and opportunities for therapeutic targets. Expert Opin. Ther. Targets 14, 693–702 (2010). sourceExperimental — accuracy not yet measured

In the paper

“Additional ligands of the HH family includes desert (DHH) and Indian (IHH) hedgehog, which also operate via primary cilia but in a tissue-specific manner, such as in cells of the testis and in growth plate chondrocytes 105, respectively.”

What the sources say

• Partly supported

  The Introduction (page not available) says vertebrate Hedgehog signaling depends on primary cilia and describes ciliary reception of Hedgehog ligands. It does not identify desert or Indian hedgehog or connect either ligand to testis cells or growth plate chondrocytes; searches for both ligand names found no such passage. (LLM, conf=0.84)

  cites [105] Mukhopadhyay, S. & Rohatgi, R. G-Protein-coupled receptors, Hedgehog signaling and primary cilia. Semin. Cell Dev. Biol. 33, 63–72 (2014). sourceExperimental — accuracy not yet measured

In the paper

“at least three — ADCY3, ADCY5, and ADCY6 — are localized to cilia 143–145.”

What the sources say

• ?Not checked — no full text of the sourcecites [143] Wong, W. & Scott, J. D. AKAP signalling complexes: focal points in space and time. Nat. Rev. Mol. Cell Biol. 5, 959–970 (2004). source
• ?Could not verify

  The Significance and Subcellular Localization of Gpr161 and PKA Subunits sections discuss recruitment of PKA to primary cilia, not localization of adenylyl cyclases. Searches for ADCY3, ADCY5, ADCY6, and ciliary adenylyl cyclases found no passage addressing the claim. (LLM, conf=0.74)

  cites [144] Bachmann, V. A. et al. Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling. Proc. Natl Acad. Sci. USA 113, 7786–7791 (2016). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [145] Mick, D. U. et al. Proteomics of primary cilia by proximity labeling. Dev. Cell 35, 497–512 (2015). source

In the paper

“Numerous GPCRs and their downstream effector molecules localize to cilia on a variety of mammalian cell types 152, 153”

What the sources say

• ?Could not verify

  The Abstract and ‘The G-protein activation cycle’ section discuss GPCR signaling and downstream effectors, but neither says they localize to cilia. Searches for cilia, ciliary localization, and mammalian cell types found no passage in our copy addressing the claimed localization. (LLM, conf=0.76)

  cites [152] Hilger, D., Masureel, M. & Kobilka, B. K. Structure and dynamics of GPCR signaling complexes. Nat. Struct. Mol. Biol. 25, 4–12 (2018). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [153] Eichel, K. & von Zastrow, M. Subcellular organization of GPCR signaling. Trends Pharmacol. Sci. 39, 200–208 (2018). source

In the paper

“The pre-ciliary function of the IFT-A core complex, together with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), in binding and ciliary trafficking of TULP3 — an adapter protein involved in the gating of ciliary GPCRs including GPR161 — explains high SHH signalling observed in IFT-A mutants, despite the presence of abnormal cilia in these models 56, 64, 122.”

What the sources say

• ?Not checked — no full text of the sourcecites [56] Qin, H. et al. Intraflagellar transport is required for the vectorial movement of TRPV channels in the ciliary membrane. Curr. Biol. 15, 1695–1699 (2005). source
• ?Not checked — no full text of the sourcecites [64] Mourão, A., Christensen, S. T. & Lorentzen, E. The intraflagellar transport machinery in ciliary signaling. Curr. Opin. Struct. Biol. 41, 98–108 (2016). source
• ?Could not verify

  The passages on Gli2 and Gli3 processing (The Efficiency of Gli2 and Gli3; Discussion, page unavailable) concern proteasomal degradation, not the proposed ciliary mechanism. Searches for IFT-A, TULP3, PI(4,5)P2, GPR161, and high Hedgehog signalling in mutants found no passage addressing the claim. (LLM, conf=0.78)

  cites [122] Pan, Y. & Wang, B. A novel protein-processing domain in Gli2 and Gli3 differentially blocks complete protein degradation by the proteasome. J. Biol. Chem. 282, 10846–10852 (2007). sourceExperimental — accuracy not yet measured

In the paper

“β-arrestins are adaptor proteins that are recruited to the proximal C-terminus of GPR161 in a manner dependent on G protein-coupled receptor kinase 2 (GRK2)138.”

What the sources say

• ?Could not verify

  The Results sections on KIF7 at growing microtubule plus-ends and ciliary tip organization discuss KIF7, microtubules, and Gli2, not GPR161 or β-arrestins (page unavailable). Searches for GPR161, β-arrestin recruitment, and GRK2 found no passage addressing the claimed interaction. (LLM, conf=0.76)

  cites [138] He, M. et al. The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment. Nat. Cell Biol. 16, 663–672 (2014). sourceExperimental — accuracy not yet measured

In the paper

“GPR161 is also removed from primary cilia in a SMO-dependent and β-arrestin-dependent manner following activation of HH signalling 28, 138.”

What the sources say

• Partly supported

  In Results (‘Ectocytosis compensates for retrieval defects’; page unavailable), the paper reports that Hedgehog activation reduces ciliary GPR161 and that β-arrestins are required for its usual retrieval. It also finds that GPR161 can still be removed by ectocytosis in β-arrestin-deficient cells, so removal is not strictly β-arrestin-dependent. The paper does not itself establish SMO dependence; that point appears in the title of the Pal et al. study in its references. (LLM, conf=0.86)

  cites [28] Nager, A. R. et al. An actin network dispatches ciliary GPCRs into extracellular vesicles to modulate signaling. Cell 168, 252–263 (2017). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Results section on Gli2 and Sufu localization reports that Smoothened moves into cilia after pathway stimulation, but does not address GPR161 leaving cilia. Searches for GPR161, ciliary exit, and β-arrestin found no passage in our copy supporting the claimed dependencies. (LLM, conf=0.76)

  cites [138] He, M. et al. The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment. Nat. Cell Biol. 16, 663–672 (2014). sourceExperimental — accuracy not yet measured

In the paper

“polycystic liver disease is a ciliopathy, characterized by the formation of fluid-filled hepatic cysts that originate from cholangiocytes 156.”

What the sources say

• ?Could not verify

  The Cholangiocyte morphology and ultrastructure section (page unavailable) says that each cholangiocyte has a primary cilium. A search for “polycystic liver disease” found it only in a reference title; searches for ciliopathies and hepatic cysts found no passage stating that the disease is a ciliopathy or that its fluid-filled cysts originate from cholangiocytes. The cited paper’s text therefore does not establish the attributed claim. (LLM, conf=0.76)

  cites [156] Tabibian, J. H., Masyuk, A. I., Masyuk, T. V., O’Hara, S. P. & LaRusso, N. F. Physiology of cholangiocytes. Compr. Physiol. 3, 541–565 (2013). sourceExperimental — accuracy not yet measured

In the paper

“the V2R receptor antagonist tolvaptan slows the decline in glomerular filtration rate in patients with ADPKD163.”

What the sources say

• ?Could not verify

  The Introduction and Discussion discuss polycystic kidney disease and the effects of dopamine and fenoldopam on renal cilia. Searches for tolvaptan, V2R or vasopressin antagonism, and decline in glomerular filtration rate found no passage addressing the claimed treatment effect in patients with ADPKD. (LLM, conf=0.76)

  cites [163] Upadhyay, V. S. et al. Roles of dopamine receptor on chemosensory and mechanosensory primary cilia in renal epithelial cells. Front. Physiol. 5, 72 (2014). sourceExperimental — accuracy not yet measured

In the paper

“The cilia-localized class A orphan GPCR, GPR161, was identified as a negative regulator of SHH signalling during early neural tube development in mice 122.”

What the sources say

• ?Could not verify

  The Abstract and Discussion address proteasomal processing of Gli2 and Gli3 in Hedgehog signalling, not GPR161. Searches for GPR161 and for its proposed role in cilia and mouse neural tube development found no passage addressing the claim; page numbers were unavailable in our copy. (LLM, conf=0.78)

  cites [122] Pan, Y. & Wang, B. A novel protein-processing domain in Gli2 and Gli3 differentially blocks complete protein degradation by the proteasome. J. Biol. Chem. 282, 10846–10852 (2007). sourceExperimental — accuracy not yet measured

In the paper

“activation of Gαi-coupled P2RY12 by its endogenous ligand, ADP, decreased forskolin-induced cAMP levels in ciliated cholangiocytes but not in non-ciliated cholangiocytes 155.”

What the sources say

• Partly supported

  The Introduction (page unavailable) reports a cilia-dependent cAMP response in cholangiocytes: TGR5 ligands decreased cAMP in ciliated cells but increased it in non-ciliated cells. It does not establish the attributed result for P2RY12 activation by ADP or for forskolin-induced cAMP; searches for those terms found no matching passage. (LLM, conf=0.78)

  cites [155] Schou, K. B., Pedersen, L. B. & Christensen, S. T. Ins and outs of GPCR signaling in primary cilia. EMBO Rep. 16, 1099–1113 (2015). sourceExperimental — accuracy not yet measured

In the paper

“overexpression of ADCYC5 and ADCYC6 partially represses the HH pathway in the developing chicken neural tube 146.”

What the sources say

• ?Could not verify

  The Results discuss AC5/6 in renal epithelial cells and its relationship to cAMP signaling, not Hedgehog signaling. Searches for Hedgehog repression and the developing chicken neural tube found no passage addressing the claimed overexpression experiment. (LLM, conf=0.76)

  cites [146] Choi, Y. H. et al. Polycystin-2 and phosphodiesterase 4C are components of a ciliary A-kinase anchoring protein complex that is disrupted in cystic kidney diseases. Proc. Natl Acad. Sci. USA 108, 10679–10684 (2011). sourceExperimental — accuracy not yet measured

In the paper

“The presence or absence of cilia might also affect GPBAR1 signalling 158.”

What the sources say

• Supported

  In “TGR5 Is a Ciliary-Associated Bile Acid Receptor,” the paper reports opposite cAMP responses to the same TGR5 agonists in ciliated and nonciliated cholangiocytes. This directly supports the hedged claim that cilia might affect GPBAR1/TGR5 signalling. (LLM, conf=0.94)

  cites [158] Masyuk, T. V., Masyuk, A. I. & LaRusso, N. F. TGR5 in the cholangiociliopathies. Dig. Dis. 33, 420–425 (2015). source

In the paper

“GRK2 and GRK3 also transduce high level SHH signals through mechanisms independent of GPR161133.”

What the sources say

• ?Could not verify

  The Results section on Dync2h1 and IFT122 reports that Shh signaling can reach high levels in certain double-mutant embryos, but it does not address GRK2, GRK3, or GPR161. Searches for those proteins and for GPR161-independent signaling found no passage supporting the attributed mechanism. Page numbers were not available in our copy. (LLM, conf=0.76)

  cites [133] Ocbina, P. J. R., Eggenschwiler, J. T., Moskowitz, I. & Anderson, K. V. Complex interactions between genes controlling trafficking in primary cilia. Nat. Genet. 43, 547–553 (2011). sourceExperimental — accuracy not yet measured

In the paper

“GPR161 regulates formation of GLI3R possibly via constitutive activation of cAMP–PKA signalling.”

What the sources say

• Partly supported

  The paper’s discussion of Gli2/Gli3 processing (Fig. 1) reports that activating PKA promotes formation of processed Gli3, and its introduction identifies processed Gli3 as a transcriptional repressor. It does not address GPR161 or show that GPR161 regulates this process through constitutive cAMP–PKA signalling. (LLM, conf=0.85)

  cites [122] Pan, Y. & Wang, B. A novel protein-processing domain in Gli2 and Gli3 differentially blocks complete protein degradation by the proteasome. J. Biol. Chem. 282, 10846–10852 (2007). sourceExperimental — accuracy not yet measured

In the paper

“Interestingly, mutations in the genes encoding TULP3 or IFT-A subunits phenocopy Gpr161 mutants by increasing HH signalling in the caudal neural tube 58, 128–131.”

What the sources say

• ?Not checked — no full text of the sourcecites [58] Behal, R. H. et al. Subunit interactions and organization of the Chlamydomonas reinhardtii intraflagellar transport complex A proteins. J. Biol. Chem. 287, 11689–11703 (2012). source
• ?Not checked — no full text of the sourcecites [128] Svard, J. et al. Genetic elimination of Suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway. Dev. Cell 10, 187–197 (2006). source
• ?Not checked — no full text of the sourcecites [129] Goodrich, L. V., Milenkovic, L., Higgins, K. M. & Scott, M. P. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277, 1109–1113 (1997). source
• Partly supported

  In “TULP3 regulates cell identity in the spinal neural tube” (page unavailable), the paper reports elevated Shh pathway activity in Tulp3 mutants, with effects limited to the lumbar neural tube; it also notes similar patterning effects in Thm1 mutants. Our copy does not compare either mutant with Gpr161 mutants or establish the claim for IFT-A subunits generally. (LLM, conf=0.86)

  cites [130] Norman, R. X. et al. Tubby-like protein 3 (TULP3) regulates patterning in the mouse embryo through inhibition of Hedgehog signaling. Hum. Mol. Genet. 18, 1740–1754 (2009). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section ('hitchhiker mutants exhibit increased Shh pathway activity during spinal neural tube closure'; page unavailable) reports increased Shh pathway activity in the caudal neural tube of Tulp3 mutants. The Discussion also mentions increased activity after loss of Thm1, but this paper does not establish that Tulp3 or IFT-A mutants phenocopy Gpr161 mutants. (LLM, conf=0.85)

  cites [131] Patterson, V. L. et al. Mouse hitchhiker mutants have spina bifida, dorso-ventral patterning defects and polydactyly: identification of Tulp3 as a novel negative regulator of the Sonic hedgehog pathway. Hum. Mol. Genet. 18, 1719–1739 (2009). sourceExperimental — accuracy not yet measured

In the paper

“removal of GPR161 from cilia upon activation of the SHH pathway is impaired in Inpp5e-knockout cells 139, 140, irrespective of levels of the pathway activator SMO”

What the sources say

• ?Not checked — no full text of the sourcecites [139] Liem, K. F. Jr., He, M., Ocbina, P. J. & Anderson, K. V. Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling. Proc. Natl Acad. Sci. USA 106, 13377–13382 (2009). source
• Partly supported

  The Discussion section (page unavailable) reports increased ciliary Gpr161 accumulation in Inpp5e knockouts, which supports the retention aspect of the claim. It does not establish that removal after SHH pathway activation is impaired in those cells irrespective of SMO levels; the Results section makes the SMO-trafficking point for β-arrestin double-knockout cells instead. (LLM, conf=0.84)

  cites [140] Pal, K. et al. Smoothened determines β-arrestin-mediated removal of the G protein-coupled receptor Gpr161 from the primary cilium. J. Cell Biol. 212, 861–875 (2016). sourceExperimental — accuracy not yet measured

In the paper

“Type 2 vasopressin receptor (V2R) which regulates Na+ and water reabsorption in the mammalian nephron has also been reported to localize to cilia on renal epithelial cells 162.”

What the sources say

• ?Could not verify

  The Results section on receptor localization reports dopamine receptor type 5 (DR5) and CaV1.2 in renal epithelial cilia, not vasopressin receptor type 2 (V2R). Searches for V2R and vasopressin receptor localization found no passage in our copy addressing the claim; page numbers were unavailable. (LLM, conf=0.76)

  cites [162] Jin, X. et al. Cilioplasm is a cellular compartment for calcium signaling in response to mechanical and chemical stimuli. Cell. Mol. Life Sci. 71, 2165–2178 (2014). sourceExperimental — accuracy not yet measured

In the paper

“ciliopathies are associated with numerous neuropathologies, including anatomical abnormalities and neuropsychiatric disorders 165.”

What the sources say

• ?Could not verify

  The Tolvaptan in Later-Stage ADPKD section describes kidney cyst development, and the Discussion addresses trial adverse events; neither addresses neuropathologies associated with ciliopathies. Searches for neuropsychiatric disorders, brain abnormalities, and related neurological terms found no passage supporting the claim. (LLM, conf=0.75)

  cites [165] Torres, V. E. et al. Tolvaptan in later-stage autosomal dominant polycystic kidney disease. N. Engl. J. Med. 377, 1930–1942 (2017). sourceExperimental — accuracy not yet measured

In the paper

“conditional disruption of cilia in adult mice causes hyperphagia and obesity 177, 178.”

What the sources say

• ?Could not verify

  The Materials and Methods (Mice; page unavailable) describe adult AC3-deficient mice, but not conditional disruption of cilia. The paper’s findings concern learning and memory; searches for hyperphagia and obesity found no passage reporting the claimed effect. Obesity appears only in the title of a different work listed in References (page unavailable). (LLM, conf=0.77)

  cites [177] Wang, Z., Phan, T. & Storm, D. R. The type 3 adenylyl cyclase is required for novel object learning and extinction of contextual memory: role of cAMP signaling in primary cilia. J. Neurosci. 31, 5557–5561 (2011). sourceExperimental — accuracy not yet measured
• Supported

  The Abstract states that the authors previously showed conditional disruption of Ift88 throughout an adult mouse leads to hyperphagia and obesity. The Results describe how cilia ablation was induced in adult mice in the present study. (LLM, conf=0.94)

  cites [178] Berbari, N. F. et al. Leptin resistance is a secondary consequence of the obesity in ciliopathy mutant mice. Proc. Natl Acad. Sci. USA 110, 7796–7801 (2013). source

In the paper

“mice lacking SSTR3, ADCY3, β-arrestin-2 or cilia in the hippocampus all show similar deficits in learning and memory 173–176”

What the sources say

• ?Could not verify

  The Results section on ciliary trafficking reports SSTR3 movement in hippocampal neurons and a role for β-arrestin-2 in SSTR3 retrieval, but not learning or memory outcomes. Searches for learning and memory deficits and for ADCY3 found no passage in our copy addressing the claimed mouse phenotypes. (LLM, conf=0.76)

  cites [173] Ye, F., Nager, A. R. & Nachury, M. V. BBSome trains remove activated GPCRs from cilia by enabling passage through the transition zone. J. Cell Biol. 217, 1847–1868 (2018). sourceExperimental — accuracy not yet measured
• Supported

  This paper supports the hippocampal-cilia part of the multi-citation sentence. The Results section ('Ift88Δ/Δ; Emx1-Cre mutants have deficits in aversive and recognition memory'; page not provided) reports impaired fear conditioning and novel object recognition after disrupting cilia in the hippocampus and cortex. It does not claim a deficit in every form of learning or memory. (LLM, conf=0.90)

  cites [174] Berbari, N. F. et al. Hippocampal and cortical primary cilia are required for aversive memory in mice. PLOS ONE 9, e106576 (2014). source
• Supported

  This paper supports the SSTR3 portion of the multi-citation sentence. Its Novel object recognition results report that sst3 knockout mice failed to show a preference for a novel object after a one-hour delay, while wild-type mice did; the Discussion specifies that spatial memory was intact. (LLM, conf=0.90)

  cites [175] Einstein, E. B. et al. Somatostatin signaling in neuronal cilia is critical for object recognition memory. J. Neurosci. 30, 4306–4314 (2010). source
• ?Not checked — no full text of the sourcecites [176] Liu, X. et al. β-arrestin-biased signaling mediates memory reconsolidation. Proc. Natl Acad. Sci. USA 112, 4483–4488 (2015). source

In the paper

“Neuronal cilia are enriched for certain GPCRs and downstream effector proteins 152, 166, 167”

What the sources say

• ?Could not verify

  The Abstract and the G-protein activation cycle section describe GPCR signaling and downstream effector proteins, but neither says they are enriched in neuronal cilia. Searches for neuronal cilia and ciliary localization found no passage addressing that claim in our copy; no page numbers were available. (LLM, conf=0.76)

  cites [152] Hilger, D., Masureel, M. & Kobilka, B. K. Structure and dynamics of GPCR signaling complexes. Nat. Struct. Mol. Biol. 25, 4–12 (2018). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [166] Wang, C. Y., Tsai, H. L., Syu, J. S., Chen, T. Y. & Su, M. T. Primary cilium-regulated EG-VEGF signaling facilitates trophoblast invasion. J. Cell. Physiol. 232, 1467–1477 (2017). source
• Partly supported

  The sections on special sensory neurons and neuronal migration describe GPCRs in neuronal cilia, including olfactory GPCRs and ciliary receptors needed for guidance-cue responses (page not provided). The copy also describes ciliary signaling, but the located passages do not establish that neuronal cilia are enriched for downstream effector proteins. (LLM, conf=0.81)

  cites [167] Guemez-Gamboa, A., Coufal, N. G. & Gleeson, J. G. Primary cilia in the developing and mature brain. Neuron 82, 511–521 (2014). sourceExperimental — accuracy not yet measured

In the paper

“Treatment of mouse hippocampal neurons with the SSTR3 ligand, somatostatin, stimulates recruitment of endogenous β-arrestin into SSTR3-positive cilia, leading to a rapid β-arrestin-2-dependent decrease in the ciliary SSTR3 167”

What the sources say

• Partly supported

  The section “Primary Cilia in the Adult Nervous System: Neurogenesis and Signaling?” states that SSTR3 is localized to neuronal cilia. It does not describe somatostatin treatment, β-arrestin recruitment, or a rapid β-arrestin-2-dependent decrease in ciliary SSTR3 (searched for somatostatin, SSTR3, and β-arrestin). (LLM, conf=0.86)

  cites [167] Guemez-Gamboa, A., Coufal, N. G. & Gleeson, J. G. Primary cilia in the developing and mature brain. Neuron 82, 511–521 (2014). sourceExperimental — accuracy not yet measured

In the paper

“Several core WNT pathway components localize to primary cilia (Figure 4) 193–197”

What the sources say

• ?Not checked — no full text of the sourcecites [193] Witte, F. et al. Negative regulation of Wnt signaling mediated by CK1-phosphorylated Dishevelled via Ror2. FASEB J. 24, 2417–2426 (2010). source
• ?Not checked — no full text of the sourcecites [194] Corbit, K. C. et al. Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms. Nat. Cell Biol. 10, 70–76 (2008). source
• ?Could not verify

  The Introduction describes the primary cilium as a signaling organelle, but does not identify WNT pathway components there. Searches for WNT and GSK3β localization found GSK3β at centrosomes or the basal body, not evidence that several core WNT components localize to primary cilia. No page numbers were available in our copy. (LLM, conf=0.73)

  cites [195] Zhang, B. et al. GSK3β-Dzip1-Rab8 cascade regulates ciliogenesis after mitosis. PLOS Biol. 13, e1002129 (2015). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Introduction describes Hedgehog pathway components localizing to primary cilia, and the Results report ciliary accumulation of Smoothened. Although the References mention CK1 in Wnt signaling, the passages found do not say that several core WNT pathway components localize to primary cilia (searched: Wnt pathway components, Wnt signaling and ciliary localization). (LLM, conf=0.76)

  cites [196] Chen, Y. et al. Sonic Hedgehog dependent phosphorylation by CK1α and GRK2 is required for ciliary accumulation and activation of Smoothened. PLOS Biol. 9, e1001083 (2011). sourceExperimental — accuracy not yet measured
• Supported

  The Introduction says several Wnt signaling components, including Inversin, localize to the ciliary/centrosomal axis. The Results (Figure 3C–G) identify Dvl-1, Dvl-3, and Frizzled-3 at primary cilia in mouse embryonic fibroblasts, directly supporting the claim. (LLM, conf=0.93)

  cites [197] Veland, I. R. et al. Inversin/Nephrocystin-2 is required for fibroblast polarity and directional cell migration. PLOS ONE 8, e60193 (2013). source

In the paper

“ciliary export of activated SSTR3 in cultured renal epithelial cells also requires β-arrestin-2 28, 172.”

What the sources say

• Partly supported

  The Results section (‘Failure to retrieve GPCRs from cilia results in ectocytosis from the tip’; page unavailable) supports a role for β-arrestin-2 in retrieving activated SSTR3 from cilia in IMCD3 kidney cells. But it also reports that activated SSTR3 exits β-arrestin-2-deficient cilia by ectocytosis, so β-arrestin-2 is not required for ciliary export in general. (LLM, conf=0.84)

  cites [28] Nager, A. R. et al. An actin network dispatches ciliary GPCRs into extracellular vesicles to modulate signaling. Cell 168, 252–263 (2017). sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion (page not provided) reports that activated GPCRs such as Sstr3 can leave ciliary tips by ectocytosis. It does not say that this export requires β-arrestin-2 or that the finding concerns cultured renal epithelial cells; the Results instead examine Sstr3 in interneurons. (LLM, conf=0.85)

  cites [172] Guo, J. et al. Primary cilia signaling shapes the development of interneuronal connectivity. Dev. Cell 42, 286–300 (2017). sourceExperimental — accuracy not yet measured

In the paper

“ciliary localization of SSTR3 is not affected in β-arrestin-2-deficient hippocampal neurons167.”

What the sources say

• Partly supported

  The section ‘Primary Cilia in the Adult Nervous System: Neurogenesis and Signaling?’ states that SSTR3 localizes to neuronal cilia (page not provided). It does not address β-arrestin-2-deficient hippocampal neurons or whether SSTR3 localization is unaffected in them; searches for those terms found no such result. (LLM, conf=0.86)

  cites [167] Guemez-Gamboa, A., Coufal, N. G. & Gleeson, J. G. Primary cilia in the developing and mature brain. Neuron 82, 511–521 (2014). sourceExperimental — accuracy not yet measured

In the paper

“mouse models of the ciliopathy BBS show dysregulation of GPCR ciliary localization.”

What the sources say

• Supported

  The paper reports that central neurons from Bbs2- or Bbs4-deficient mice have apparently normal primary cilia but lack ciliary localization of the GPCRs Sstr3 and Mchr1. The Results also report no detectable Mchr1-positive cilia in the examined brain regions of those mice, directly supporting the claim. (LLM, conf=0.94)

  cites [73] Berbari, N. F., Lewis, J. S., Bishop, G. A., Askwith, C. C. & Mykytyn, K. Bardet-Biedl syndrome proteins are required for the localization of G protein-coupled receptors to primary cilia. Proc. Natl Acad. Sci. USA 105, 4242–4246 (2008). source
• ?Not checked — no full text of the sourcecites [74] Loktev, A. V. & Jackson, P. K. Neuropeptide Y family receptors traffic via the Bardet-Biedl syndrome pathway to signal in neuronal primary cilia. Cell Rep. 5, 1316–1329 (2013). source
• ?Not checked — no full text of the sourcecites [168] Green, J. A. et al. Recruitment of β-arrestin into neuronal cilia modulates somatostatin receptor subtype 3 ciliary localization. Mol. Cell. Biol. 36, 223–235 (2016). source

In the paper

“agonist-dependent ciliary export of heterologously-expressed SSTR3 in inner medullary collecting duct cells lacking either BBSome function or β-arrestin-2, involved active recruitment of SSTR3 to the ciliary tip from where a considerable fraction was released in ectosomes 28.”

What the sources say

• Supported

  The Results section on failed GPCR retrieval reports that agonist-treated IMCD3 cells lacking BBSome components or β-arrestin-2 accumulate SSTR3 at ciliary tips and release SSTR3-containing ectosomes. The Results section on selective losses reports that ectosomes from somatostatin-treated β-arrestin-2-deficient cells contained 49% of ciliary SSTR3. Page numbers are unavailable in our copy. (LLM, conf=0.94)

  cites [28] Nager, A. R. et al. An actin network dispatches ciliary GPCRs into extracellular vesicles to modulate signaling. Cell 168, 252–263 (2017). source

In the paper

“Similarly, RPGRIP1L regulates WNT–PCP pathways by modulating DVL levels 212, 215.”

What the sources say

• Supported

  The Results section, “Rpgrip1l acts in PCP by stabilizing dishevelled,” reports reduced Dvl2 levels after rpgrip1l knockdown and rescue of planar-polarity-related defects by dishevelled expression. The paper concludes that Rpgrip1l acts in these processes at least partly by stabilizing Dvl, supporting the cited paraphrase. (LLM, conf=0.91)

  cites [212] Mahuzier, A. et al. Dishevelled stabilization by the ciliopathy protein Rpgrip1l is essential for planar cell polarity. J. Cell Biol. 198, 927–940 (2012). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The paper’s Wnt-signalling passages discuss Jade-1, pVHL and β-catenin in canonical Wnt signalling, not RPGRIP1L or WNT–PCP. Searches for RPGRIP1L, DVL/Dishevelled and planar cell polarity found no passage in our copy addressing the claimed mechanism. No page numbers were provided for these passages. (LLM, conf=0.75)

  cites [215] Chitalia, V. C. et al. Jade-1 inhibits Wnt signaling by ubiquitinating β-catenin and mediates Wnt pathway inhibition by pVHL. Nat. Cell Biol. 10, 1208–1216 (2008). sourceExperimental — accuracy not yet measured

In the paper

“in lung cancer cell lines, KIF3A restricts WNT canonical signalling, but independently of the primary cilium by restricting β-arrestin interaction with DVL2 and AXIN as well by modulating WNT ligand secretion 201.”

What the sources say

• ?Could not verify

  The Results section on Axin2 expression reports no detectable change in canonical Wnt signaling in Kif3a-mutant mouse embryos. The fibroblast Results section likewise concerns responses to added Wnt3a, not lung cancer cells. Searches for β-arrestin interactions and Wnt ligand secretion found no passage addressing the claimed KIF3A mechanism; the embryo findings do not establish what happens in lung cancer cells. (LLM, conf=0.78)

  cites [201] Ocbina, P. J. R., Tuson, M. & Anderson, K. V. Primary cilia are not required for normal canonical Wnt signaling in the mouse embryo. PLOS ONE 4, e6839 (2009). sourceExperimental — accuracy not yet measured

In the paper

“A series of other RTKs, including epidermal growth factor receptor (EGFR) 224, 225, fibroblast growth factor receptor 3 (FGFR3) 226, tropomyosin receptor kinase B (TRKB, also known as neurotrophic tyrosine kinase receptor 2 227 and angiopoetin-1 receptor (TIE2) 228 also localize to primary cilia.”

What the sources say

• Partly supported

  The “Additional RTKs Associated with Primary Cilia” section (page not provided) reports EGFR on primary cilia and Tie2 on primary cilia in murine reproductive tissues. It discusses FGFRs as a group at the basal body of primary cilia, not FGFR3 specifically on primary cilia, and does not identify TRKB as ciliary. (LLM, conf=0.88)

  cites [224] Christensen, S. T., Morthorst, S. K., Mogensen, J. B. & Pedersen, L. B. Primary cilia and coordination of receptor tyrosine kinase (RTK) and transforming growth factor beta (TGF-β) signaling. Cold Spring Harb. Perspect. Biol. 9, a028167 (2017). sourceExperimental — accuracy not yet measured
• Supported

  The citation is attached to EGFR, not to the other receptors in the list. The Results section reports that native EGFR colocalizes with PKD2 in the primary cilium of LLC-PK1 cells (Fig. 8). (LLM, conf=0.94)

  cites [225] Ma, R. et al. PKD2 functions as an epidermal growth factor-activated plasma membrane channel. Mol. Cell. Biol. 25, 8285–8298 (2005). source
• ?Not checked — no full text of the sourcecites [226] Danilov, A. I. et al. Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zone. Glia 57, 136–152 (2009). source
• ?Not checked — no full text of the sourcecites [227] Martin, L. et al. Constitutively-active FGFR3 disrupts primary cilium length and IFT20 trafficking in various chondrocyte models of achondroplasia. Hum. Mol. Genet. 27, 1–13 (2018). source

In the paper

“Indeed a key manner by which cilia might regulate WNT pathway components is through direct proteasomal degradation 212, 216, 217”

What the sources say

• Supported

  The Introduction (page unavailable) says the basal-body protein inversin targets the Wnt component dishevelled for proteasomal degradation. The Results (page unavailable) also show that inhibiting the proteasome restores dishevelled levels after RPGRIP1L depletion, supporting the hedged claim that cilia-associated proteins may regulate Wnt components through this mechanism. (LLM, conf=0.90)

  cites [212] Mahuzier, A. et al. Dishevelled stabilization by the ciliopathy protein Rpgrip1l is essential for planar cell polarity. J. Cell Biol. 198, 927–940 (2012). source
• Supported

  The Results section reports that loss of the ciliary protein Rpgrip1l reduces proteasomal activity at the ciliary base and increases phospho-β-catenin there. It identifies β-catenin as a Wnt pathway component and proteasomal substrate, supporting the citing sentence’s hedged mechanism. No page number is available in our copy. (LLM, conf=0.92)

  cites [216] Gerhardt, C. et al. The transition zone protein Rpgrip1l regulates proteasomal activity at the primary cilium. J. Cell Biol. 210, 1027 (2015). source
• ?Not checked — no full text of the sourcecites [217] Gerdes, J. M. et al. Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response. Nat. Genet. 39, 1350–1360 (2007). source

In the paper

“Designated subtypes of class II and class III RTKs, including platelet-derived growth factor alpha receptor (PDFGRα), the insulin receptor (IR) and insulin-like growth factor receptor (IGFIR) operate in primary cilia to control specific processes in cells and tissues 222, 223”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [222] Crudden, C. et al. in International Review of Cell and Molecular Biology Vol. 339. (ed. Shukla, A. K.) 1–40 (Academic Press, 2018).
• Partly supported

  The RTK overview and the PDGFRα and IGF-1R signalling sections describe PDGFRα and IGF1R signalling through primary cilia in cell migration, cell-cycle control, and differentiation. The IGF-1R section mentions IR as a related receptor and a kinase that targets IRS-1, but does not say IR operates in primary cilia. The cited passages also do not specify the class II/III designations; page numbers are unavailable in our copy. (LLM, conf=0.85)

  cites [223] Christensen, S. T., Clement, C. A., Satir, P. & Pedersen, L. B. Primary cilia and coordination of receptor tyrosine kinase (RTK) signalling. J. Pathol. 226, 172–184 (2012). sourceExperimental — accuracy not yet measured

In the paper

“the cystic kidney and abnormal brain development phenotypes of mice deficient in JBN are largely caused by dysregulated WNT–β-catenin signalling 207.”

What the sources say

• Partly supported

  The discussion (page unavailable) says Ahi1/Jbn-mutant mice have Wnt defects in specific tissues and at defined stages, and cites prior findings on renal homeostasis. But it also says severe developmental Wnt phenotypes are spared and embryonic Wnt activity is grossly normal in most tissues. It does not establish that Wnt dysregulation largely causes both the cystic kidney and abnormal brain-development phenotypes. (LLM, conf=0.84)

  cites [207] Lancaster, M. A., Schroth, J. & Gleeson, J. G. Subcellular spatial regulation of canonical Wnt signalling at the primary cilium. Nat. Cell Biol. 13, 700 (2011). sourceExperimental — accuracy not yet measured

In the paper

“In vitro, NPHP2 controlled fibroblast polarity and directional cell motility through modulation of ciliary WNT signalling pathways that control the activity and localization of polarity proteins to the leading edge of migrating cells 196.”

What the sources say

• ?Could not verify

  The Results section on the kinesin-II ciliary motor discusses Sonic Hedgehog–induced Smoothened phosphorylation and conformation in fibroblasts, not NPHP2-dependent polarity or migration. Searches for NPHP2, directional cell motility, and WNT-dependent localization of polarity proteins to the leading edge found no passage addressing the claim; Wnt appears in a reference title. (LLM, conf=0.78)

  cites [196] Chen, Y. et al. Sonic Hedgehog dependent phosphorylation by CK1α and GRK2 is required for ciliary accumulation and activation of Smoothened. PLOS Biol. 9, e1001083 (2011). sourceExperimental — accuracy not yet measured

In the paper

“evidence suggests that other NPHP module components including NPHP3 209, NPHP4 210 and RPGRIP1L (PMID 22927466, 212) modulate the WNT pathway through DVL.”

What the sources say

• ?Could not verify

  The Results report that RPGRIP1L colocalises with ROR2, a non-canonical Wnt-signalling protein, but do not show that RPGRIP1L modulates Wnt signalling through DVL. The Introduction discusses DVL in planar cell polarity signalling without linking it to RPGRIP1L, NPHP3 or NPHP4; searches for those proteins and DVL found no passage making the claimed connection. The supplied copy gives no page numbers. (LLM, conf=0.75)

  cites [209] Abdelhamed, Z. A. et al. The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning and epithelial branching morphogenesis in mice via the non-canonical Wnt pathway. Dis. Model. Mech. 8, 527–541 (2015). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [210] Bergmann, C. et al. Loss of nephrocystin-3 function can cause embryonic lethality, Meckel-Gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia. Am. J. Hum. Genet. 82, 959–970 (2008). source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites PMID 22927466, 212

In the paper

“Thus, despite intense investigation, the function of the primary cilium in fine-tuning WNT signalling remains unclear 204.”

What the sources say

• Supported

  The Introduction (p. 1) says it remains controversial whether cilia affect Wnt signaling, supporting the claim that their role is unclear. The paper's Conclusions (p. 9) narrow its own finding to a study suggesting that cilia are not involved in Wnt signaling; that does not resolve the broader uncertainty described in the citing sentence. (LLM, conf=0.86)

  cites [204] Huang, P. & Schier, A. F. Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia. Development 136, 3089–3098 (2009). source

In the paper

“mouse embryos and mouse embryonic fibroblasts with mutations in Kif3a, Ift88, Ift72 and a gene that encodes a component of dynein-2 (Dync2h1) exhibited normal Axin2 mRNA expression and canonical WNT reporter activity 200.”

What the sources say

• ?Could not verify

  The Results report unchanged axin2 expression after Inversin depletion in Xenopus pronephroi, not in mouse embryos or embryonic fibroblasts. Searches for Kif3a, Ift88, Ift72, Dync2h1, and canonical WNT reporter activity found no passage addressing the claimed mouse experiments. (LLM, conf=0.76)

  cites [200] Lienkamp, S. et al. Inversin relays Frizzled-8 signals to promote proximal pronephros development. Proc. Natl Acad. Sci. USA 107, 20388–20393 (2010). sourceExperimental — accuracy not yet measured

In the paper

“Conversely, feedback inhibitors of TGFβ/BMP signalling, including SMAD7 and SMURF1 265, 288, localize to the ciliary base 268, 273 and restrain excessive signalling from the primary cilium.”

What the sources say

• ?Not checked — no full text of the sourcecites [265] Nickel, J., ten Dijke, P. & Mueller, T. D. TGF-β family co-receptor function and signaling. Acta Biochim. Biophys. Sin. 50, 12–36 (2018). source
• ?Could not verify

  The Discussion says TSC1 localizes to the ciliary base, and the Results describe SMAD2/3 activation near that region. Searches for SMAD7, SMURF1, and feedback inhibition found no passage in our copy saying those inhibitors localize there or restrain ciliary TGFβ/BMP signaling. No page numbers were available in the indexed copy. (LLM, conf=0.73)

  cites [288] Rosengren, T., Larsen, L. J., Pedersen, L. B., Christensen, S. T. & Møller, L. B. TSC1 and TSC2 regulate cilia length and canonical Hedgehog signaling via different mechanisms. Cell. Mol. Life Sci. 75, 2663–2680 (2018). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [268] Bakkebø, M. et al. SARA is dispensable for functional TGF-β signaling. FEBS Lett. 586, 3367–3372 (2012). source
• Partly supported

  The Discussion (page unavailable) reports that a ceramide–Smad7 complex inhibits TGF-β receptor trafficking and signaling at primary cilia. It does not establish that SMAD7 localizes to the ciliary base, or address SMURF1 or BMP signaling; the Introduction instead describes Smurf2. (LLM, conf=0.86)

  cites [273] Gencer, S. et al. TGF-β receptor I/II trafficking and signaling at primary cilia are inhibited by ceramide to attenuate cell migration and tumor metastasis. Sci. Signal. 10, eaam7464 (2017). sourceExperimental — accuracy not yet measured

In the paper

“The sensory capacity of primary cilia relies on the coordinated trafficking and temporal localization of specific receptors and associated signal transduction modules in the cilium.”

In the paper

“In this review we highlight central mechanisms by which primary cilia coordinate HH, G-protein-coupled receptor, WNT, receptor tyrosine kinase and TGFβ/BMP signalling, and illustrate how defects in the balanced output of ciliary signalling events are coupled to developmental disorders and disease progression.”

In the paper

“Primary cilia are dynamic organelles that are assembled and disassembled in coordination with cell cycle and developmental cues.”

In the paper

“The length of cilia is controlled by the actions of various kinases and other proteins 7, 8;”

What the sources say

• ?Not checked — no full text of the sourcecites [7] Avasthi, P. & Marshall, W. F. Stages of ciliogenesis and regulation of ciliary length. Differentiation 83, S30–42 (2012). source
• ?Not checked — no full text of the sourcecites [8] Broekhuis, J. R., Leong, W. Y. & Jansen, G. Regulation of cilium length and intraflagellar transport. Int. Rev. Cell. Mol. Biol. 303, 101–138 (2013). source

In the paper

“Consistent with important roles for primary cilia in signalling, mutations that lead to their dysfunction underlie a pleiotropic group of diseases and syndromic disorders termed ciliopathies, which affect many different tissues and organs of the body.”

What the sources say

• ?Not checked — no full text of the sourcecites [2] Kenny, T. D. & Beales, P. L. (eds) Ciliopathies: A Reference for Clinicians (Oxford Univ. Press, 2014). source

In the paper

“whereas basal feet interact with the actin cytoskeleton of the cell to regulate basal body alignment in cells that contain multiple motile cilia, such as epithelial cells that line the mammalian respiratory tract, brain ventricles or oviduct 6.”

What the sources say

• ?Not checked — no full text of the sourcecites [6] Meunier, A. & Azimzadeh, J. Multiciliated cells in animals. Cold Spring Harb. Perspect. Biol. 8, a028233 (2016). source

In the paper

“Both motile and non-motile cilia, including primary cilia, comprise a microtubule-based axoneme that extends from a basal body and is covered by a bilayer lipid membrane enriched in specific signalling receptors and ion channels.”

In the paper

“The canonical hedgehog (HH) pathway, for example, is a bona fide ciliary signalling system that regulates cell fate and self-renewal in development and tissue homeostasis.”

What the sources say

• ?Not checked — no full text of the sourcecites [95] Su, Q. et al. Structure of the human PKD1-PKD2 complex. Science 361, eaat9819 (2018). source
• ?Not checked — no full text of the sourcecites [97] Huangfu, D. et al. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426, 83–87 (2003). source

In the paper

“Cilia are unable to synthesize proteins; therefore, cilia-associated transport pathways also function during cilium biogenesis and maintenance by delivering the building blocks required for ciliary axoneme and”

In the paper

“In addition to gating by the TZ and basal body transition fibres, ciliary composition and function are also regulated by active transport mechanisms (Figure 1).”

In the paper

“Between the basal body and cilium proper is a region known as the ciliary transition zone (TZ), which contains specialized gating structures such as Y-links that along with the basal body transition fibres control the entrance and exit of ciliary proteins, and thereby contribute to compartmentalization of the organelle (Figure 1).”

In the paper

“In agreement with these observations, PC1 and PC2 were found to localize to primary cilia in mammalian cells such as those of the renal collecting duct 82–84.”

What the sources say

• ?Not checked — no full text of the sourcecites [82] Yoder, B. K., Hou, X. & Guay-Woodford, L. M. The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J. Am. Soc. Nephrol. 13, 2508–2516 (2002). source
• ?Not checked — no full text of the sourcecites [83] Pazour, G. J., San Agustin, J. T., Follit, J. A., Rosenbaum, J. L. & Witman, G. B. Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease. Curr. Biol. 12, R378–R380 (2002). source
• ?Not checked — no full text of the sourcecites [84] Nauli, S. M. et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 33, 129–137 (2003). source

In the paper

“the primary cilium is now known to be fundamentally important for canonical SHH signalling in vertebrates 97.”

What the sources say

• ?Not checked — no full text of the sourcecites [97] Huangfu, D. et al. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426, 83–87 (2003). source

In the paper

“Defects in IFT were first shown to disrupt sonic hedgehog (SHH) signalling during mouse embryonic development in a forward genetic screen in 2003 96;”

What the sources say

• ?Not checked — no full text of the sourcecites [96] Briscoe, J. & Thérond, P. P. The mechanisms of Hedgehog signalling and its roles in development and disease. Nat. Rev. Mol. Cell Biol. 14, 416 (2013). source

In the paper

“The final transcriptional output of canonical HH signalling is determined by post-translational modifications of GLI transcription factors, which cause intracellular activation or basal repression of pathway targets in the presence or absence of HH morphogens, respectively.”

In the paper

“Inactive SMO is stabilized by a π-cation lock in the inner transmembrane interface.”

In the paper

“HH signalling pathways regulate a number of cell fate and self-renewal processes in development and tissue homeostasis 95.”

What the sources say

• ?Not checked — no full text of the sourcecites [95] Su, Q. et al. Structure of the human PKD1-PKD2 complex. Science 361, eaat9819 (2018). source

In the paper

“Furthermore, mutations in PKD2 have been linked to left-right laterality defects in vertebrates, including humans (add refs: PMID 12062060 and PMID 21719175).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites PMID 12062060
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites PMID 21719175

In the paper

“suggesting that a number of factors are responsible for the dynamic regulation of HH signalling components in cilia.”

In the paper

“The distal C-tail of GPR161 has a conserved amphipathic helix that directly binds to type I PKA regulatory subunits 142”

What the sources say

• ?Not checked — no full text of the sourcecites [142] Chavez, M. et al. Modulation of ciliary phosphoinositide content regulates trafficking and Sonic Hedgehog signaling output. Dev. Cell 34, 338–350 (2015). source

In the paper

“These findings therefore suggest that GPCR-mediated cAMP signalling in cholangiocyte cilia is distinct from cAMP signalling on the plasma membrane of cholangiocytes.”

In the paper

“Thus, IFT-A-regulated trafficking of TULP3 and GPR161 regulates basal suppression of SHH signalling.”

In the paper

“the type I PKA regulatory subunit alpha localizes to cilia 143”

What the sources say

• ?Not checked — no full text of the sourcecites [143] Wong, W. & Scott, J. D. AKAP signalling complexes: focal points in space and time. Nat. Rev. Mol. Cell Biol. 5, 959–970 (2004). source

In the paper

“suggesting that cholangiocyte cilia mediate cAMP signalling in response to biliary factors.”

In the paper

“the EG-VEGF receptor, prokineticin receptor 1 (PROKR1) localizes to cilia on human trophoblast cell lines and human first-trimester placental tissue 164.”

What the sources say

• ?Not checked — no full text of the sourcecites [164] Raychowdhury, M. K. et al. Vasopressin receptor-mediated functional signaling pathway in primary cilia of renal epithelial cells. Am. J. Physiol. Renal Physiol. 296, F87–F97 (2009). source

In the paper

“A clear link also exists between cilia dysfunction and cystic kidney disease 159.”

What the sources say

• ?Not checked — no full text of the sourcecites [159] Keitel, V., Ullmer, C. & Haussinger, D. The membrane-bound bile acid receptor TGR5 (Gpbar-1) is localized in the primary cilium of cholangiocytes. Biol. Chem. 391, 785–789 (2010). source

In the paper

“Studies from the past few years suggest that active suppression of HH pathway is as important as activation of the pathway during development and in maintenance of tissue homeostasis.”

In the paper

“Most components of canonical HH signalling are dynamically associated with cilia.”

In the paper

“tubby mice, which carry a mutation in the gene encoding the TUB protein and display ciliopathy phenotypes, exhibit defective localization of a number of GPCRs in neuronal cilia 74, 169.”

What the sources say

• ?Not checked — no full text of the sourcecites [74] Loktev, A. V. & Jackson, P. K. Neuropeptide Y family receptors traffic via the Bardet-Biedl syndrome pathway to signal in neuronal primary cilia. Cell Rep. 5, 1316–1329 (2013). source
• ?Not checked — no full text of the sourcecites [169] Domire, J. S. et al. Dopamine receptor 1 localizes to neuronal cilia in a dynamic process that requires the Bardet-Biedl syndrome proteins. Cell. Mol. Life Sci. 68, 2951–2960 (2011). source

In the paper

“NPY2R localizes to cilia on hypothalamic neurons in mice 74.”

What the sources say

• ?Not checked — no full text of the sourcecites [74] Loktev, A. V. & Jackson, P. K. Neuropeptide Y family receptors traffic via the Bardet-Biedl syndrome pathway to signal in neuronal primary cilia. Cell Rep. 5, 1316–1329 (2013). source

In the paper

“conditional disruption of ARL13B, which is a GTPase required for proper ciliary signalling, in post-migratory interneurons perturbs circuit development in the mouse striatum 171.”

What the sources say

• ?Not checked — no full text of the sourcecites [171] Marin, O. Interneuron dysfunction in psychiatric disorders. Nat. Rev. Neurosci. 13, 107–120 (2012). source

In the paper

“suggesting that ciliary export of activated SSTR3 is mediated by β-arrestin-2.”

In the paper

“suggesting that receptor ciliary localization is required for ligand-dependent signalling in vivo.”