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

In the paper

“Ciliary JBN facilitates the ciliary localization of β-catenin following WNT3A stimulation and thereby negatively affects WNT signalling 206.”

What the sources say

• Disputed

  In Results, ‘Jbn facilitates β-catenin nuclear translocation’ (page unavailable), the paper reports that Jbn enhances Wnt3a-dependent β-catenin accumulation in the nucleus, not the cilium. In Results, ‘Jbn functions downstream of β-catenin stabilization’ (page unavailable), it reports that Jbn potentiates the response to Wnt3a and positively modulates canonical Wnt signaling, contrary to the claimed negative effect. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  cites [206] Lancaster, M. A. et al. Impaired Wnt–β-catenin signaling disrupts adult renal homeostasis and leads to cystic kidney ciliopathy. Nat. Med. 15, 1046 (2009). sourceExperimental — accuracy not yet measured

In the paper

“Dopamine receptor type 5 (D5) localizes to cilia on renal epithelial cells, where it may functionally couple to the CaV1.2 L-type calcium channel 160.”

What the sources say

• ?Could not verify

  The Abstract and Discussion describe TGR5 localization and signaling in cholangiocyte cilia, not dopamine receptor D5 in renal epithelial cilia. Searches for D5 and CaV1.2 found no passage addressing their localization or functional coupling; the Discussion mentions renal epithelial cilia only in relation to cAMP signaling. No page numbers were provided in our copy. (LLM, conf=0.76)

  cites [160] Masyuk, A. I. et al. Ciliary subcellular localization of TGR5 determines the cholangiocyte functional response to bile acid signaling. Am. J. Physiol. Gastrointest. Liver Physiol. 304, G1013–G1024 (2013). sourceExperimental — accuracy not yet measured

In the paper

“For cells that form a single primary cilium (Figure 1), the basal body is derived from the mother centriole of the centrosome, and depending on the cell type, axoneme extension can be initiated before or after docking of the basal body at the plasma membrane 4, 5.”

What the sources say

• Partly supported

  Phase II (pp. 369–370) describes a ciliary shaft growing from one centriole before the cilium reaches the cell surface. The discussion (p. 374) contrasts this with a reported neuroepithelial sequence in which the centriole first attaches to the cell membrane. The paper does not identify the cilium-forming centriole as the mother centriole, and its description of shaft growth does not establish when axoneme extension begins. (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

“Quiescent cells can lose their cilium as a consequence of developmental programming 15–19 or in response to environmental insults such as mechanical stress 20.”

What the sources say

• Partly supported

  The Abstract and a main-text passage indexed under Abstract (page unavailable) show that apical abscission dismantles the primary cilium during neuronal differentiation. They place cilium disassembly before cell-cycle exit, however, so the paper does not establish cilium loss in already quiescent cells. The mechanical-stress clause has a separate citation and is not attributed to this source. (LLM, conf=0.88)

  cites [15] Das, R. M. & Storey, K. G. Apical abscission alters cell polarity and dismantles the primary cilium during neurogenesis. Science 343, 200–204 (2014). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The citation to this paper is attached to the claim that mechanical stress can cause quiescent cells to lose their cilium. The Results and Discussion describe reduced cilia in mice with an IFT88 mutation and developmental regression of cilia in rodent ear hair cells, but the passages found by searching for mechanical stress and environmental insults do not address stress-induced cilium loss. (LLM, conf=0.77)

  cites [16] McDermott, K. M., Liu, B. Y., Tlsty, T. D. & Pazour, G. J. Primary cilia regulate branching morphogenesis during mammary gland development. Curr. Biol. 20, 731–737 (2010). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [17] Blitzer, A. L. et al. Primary cilia dynamics instruct tissue patterning and repair of corneal endothelium. Proc. Natl Acad. Sci. USA 108, 2819–2824 (2011). source
• Partly supported

  The Discussion (page unavailable) says cilia formation is controlled by stable lineage-based mechanisms and that visceral endoderm and XEN cells fail to form cilia. This supports developmental control of ciliation, but the paper does not establish that quiescent cells lose a cilium they previously had. The mechanical-stress clause has a separate citation and is not assessed against this source. (LLM, conf=0.84)

  cites [18] Bangs, F. K., Schrode, N., Hadjantonakis, A. K. & Anderson, K. V. Lineage specificity of primary cilia in the mouse embryo. Nat. Cell Biol. 17, 113–122 (2015). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The citation range 15–19 is attached to developmental programming; mechanical stress has a separate citation (20). The Results section, “Primary Cilium Induction Helps Generate Fully Mature and Functional hiPSC-Derived RPE” (page unavailable), says cilia emerge as RPE cells mature, but does not say quiescent cells lose cilia through developmental programming. Searches for cilium loss and quiescence found no passage establishing that point. (LLM, conf=0.72)

  cites [19] May-Simera, H. L. et al. Primary cilium-mediated retinal pigment epithelium maturation is disrupted in ciliopathy patient cells. Cell Rep. 22, 189–205 (2018). sourceExperimental — accuracy not yet measured
• Supported

  The Results and discussion report that primary cilia in confluent human endothelial cell cultures disassembled after two hours of laminar shear stress. This supports the mechanical-stress portion attributed to this source; the developmental-programming portion is cited to other sources. (LLM, conf=0.92)

  cites [20] Iomini, C., Tejada, K., Mo, W., Vaananen, H. & Piperno, G. Primary cilia of human endothelial cells disassemble under laminar shear stress. J. Cell Biol. 164, 811–817 (2004). source

In the paper

“before mitosis the cilium is usually dismantled and centrioles are duplicated for participation in mitotic spindle pole formation 9–14.”

What the sources say

• ?Not checked — no full text of the sourcecites [9] Tucker, R. W., Pardee, A. B. & Fujiwara, K. Centriole ciliation is related to quiescence and DNA synthesis in 3T3 cells. Cell 17, 527–535 (1979). source
• ?Not checked — no full text of the sourcecites [10] Rieder, C. L., Jensen, C. G. & Jensen, L. C. The resorption of primary cilia during mitosis in a vertebrate (PtK1) cell line. J. Ultrastruct. Res. 68, 173–185 (1979). source
• ?Not checked — no full text of the sourcecites [11] Tucker, R. W., Scher, C. D. & Stiles, C. D. Centriole deciliation associated with the early response of 3T3 cells to growth factors but not to SV40. Cell 18, 1065–1072 (1979). source
• Partly supported

  The Introduction says that in many cells cilia are resorbed at mitotic entry, supporting the cilium-disassembly part of the claim. It identifies the basal body as arising from a centriole, but does not say that centrioles are duplicated for mitotic spindle pole formation. (LLM, conf=0.86)

  cites [12] Pugacheva, E. N., Jablonski, S. A., Hartman, T. R., Henske, E. P. & Golemis, E. A. HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 129, 1351–1363 (2007). sourceExperimental — accuracy not yet measured
• Supported

  The Introduction (page unavailable) says primary cilia are normally absent during mitosis, describes disassembly at the G2/M transition, and links release of the mother centriole to spindle formation. The Results (page unavailable) identify duplicated centrosomes before mitosis and report that cilia are typically absent by centrosome separation. (LLM, conf=0.86)

  cites [13] Spalluto, C., Wilson, D. I. & Hearn, T. Evidence for reciliation of RPE1 cells in late G1 phase, and ciliary localisation of cyclin B1. FEBS Open Bio 3, 334–340 (2013). source
• Supported

  The Results (Figure 2 caption; page unavailable) describe a cilium being disassembled shortly before mitosis. The Introduction identifies centrioles as components of centrosomes at mitotic spindle poles, and the Discussion describes centriole duplication before spindle formation. The paper also notes that cilia can persist during centriole duplication, so dismantling is not a prerequisite for duplication. (LLM, conf=0.90)

  cites [14] Ford, M. J. et al. A cell/cilia cycle biosensor for single-cell kinetics reveals persistence of cilia after G1/S transition is a general property in cells and mice. Dev. Cell 47, 509–523 (2018). source

In the paper

“The three dimensional structures of many IFT-B polypeptides have been solved, and progress has been made towards understanding the arrangement and interactions of individual IFT polypeptides within the IFT-A and IFT-B sub-complexes 25.”

What the sources say

• Supported

  The IFT-B core architecture section describes several solved crystal structures of IFT-B subcomplexes and a domain-level map of interactions among their proteins. The IFT-A architecture section reports identified core and noncore interactions. The paper also notes that the overall positions of proteins remain uncertain, consistent with the claim’s description of progress rather than a complete arrangement. (LLM, conf=0.89)

  cites [25] Taschner, M. & Lorentzen, E. The intraflagellar transport machinery. Cold Spring Harb. Perspect. Biol. 8, a028092 (2016). sourceExperimental — accuracy not yet measured

In the paper

“Subsequent work in a range of additional organisms, including protists such as Tetrahymena thermophila and Trypanosoma brucei and metazoans like C. elegans, sea urchin, zebrafish, mouse, and human, have substantiated this view, and provided remarkable insight into the molecular workings and physiological roles of IFT 25, 30, 31, 46.”

What the sources say

• Partly supported

  The paper’s discovery and IFT-A sections describe IFT findings in Tetrahymena, Trypanosoma, C. elegans, zebrafish and mammals, including molecular functions and disease relevance (page unavailable in our copy). Its only sea-urchin mention is a reference to a kinesin purified from sea-urchin eggs; it does not describe sea-urchin work substantiating IFT conservation or clarifying IFT’s roles. (LLM, conf=0.84)

  cites [25] Taschner, M. & Lorentzen, E. The intraflagellar transport machinery. Cold Spring Harb. Perspect. Biol. 8, a028092 (2016). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [30] Pedersen, L. B. & Rosenbaum, J. L. Intraflagellar transport (IFT) role in ciliary assembly, resorption and signalling. Curr. Top. Dev. Biol. 85, 23–61 (2008). source
• Partly supported

  Section 7 (IFT in different Model Systems; page unavailable) describes IFT studies across protists, C. elegans, sea urchins, zebrafish, and mice, and says direct assays in several systems have yielded mechanistic insight. Its Protists subsection covers Trypanosoma, and its references identify an IFT assay in Tetrahymena. The passages support the broad cross-eukaryote point, but do not document human work as part of the claimed subsequent studies. (LLM, conf=0.82)

  cites [31] Prevo, B., Scholey, J. M. & Peterman, E. J. G. Intraflagellar transport: mechanisms of motor action, cooperation, and cargo delivery. FEBS J. 284, 2905–2931 (2017). sourceExperimental — accuracy not yet measured

In the paper

“For example, although early work using C. reinhardtii and C. elegans mutants suggested that IFT-A and IFT-B complexes function in retrograde and anterograde IFT, respectively 30, 46, we now know that these polypeptides participate in ciliary transport in both directions 54–60.”

What the sources say

• ?Not checked — no full text of the sourcecites [30] Pedersen, L. B. & Rosenbaum, J. L. Intraflagellar transport (IFT) role in ciliary assembly, resorption and signalling. Curr. Top. Dev. Biol. 85, 23–61 (2008). source
• ?Not checked — no full text of the sourcecites [46] Rosenbaum, J. L. & Witman, G. B. Intraflagellar transport. Nat. Rev. Mol. Cell Biol. 3, 813–825 (2002). source
• ?Not checked — no full text of the sourcecites [54] Perkins, L. A., Hedgecock, E. M., Thomson, J. N. & Culotti, J. G. Mutant sensory cilia in the nematode Caenorhabditis elegans. Dev. Biol. 117, 456–487 (1986). source
• ?Not checked — no full text of the sourcecites [55] Pedersen, L. B. et al. Chlamydomonas IFT172 is encoded by FLA11, interacts with CrEB1, and regulates IFT at the flagellar tip. Curr. Biol. 15, 262–266 (2005). source
• ?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
• Partly supported

  In “TULP3 is an effector of the IFT-A complex” (page unavailable), the paper says IFT-A provides ciliary access to TULP3 in addition to its known retrograde role, supporting a role for IFT-A in both directions. The introductory discussion describes IFT-B proteins accumulating when retrograde transport is impaired, but does not establish that IFT-B itself functions in both directions. (LLM, conf=0.82)

  cites [57] Mukhopadhyay, S. et al. TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia. Genes Dev. 24, 2180–2193 (2010). sourceExperimental — accuracy not yet measured
• ?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
• Partly supported

  The Discussion section “IFT144 is required for anterograde, as well as retrograde, ciliary trafficking” supports a role for IFT-A in both directions and describes IFT-B as participating in anterograde trafficking. It does not establish that IFT-B participates in retrograde trafficking, so it supports only part of the claim attributed to this source. Page numbers were not available in our copy. (LLM, conf=0.82)

  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
• Supported

  The Discussion (page unavailable) says the view that IFT-B is predominantly anterograde and IFT-A predominantly retrograde is overly simplistic. It reports that loss of the IFT-B subunit IFT25 impairs ciliary export, supporting the bidirectional-transport point for which this paper is cited. The earlier mutant work is attributed to other citations in the sentence. (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). source

In the paper

“We now know these polypeptides can be subdivided into IFT-A, IFT-B1 and IFT-B2 sub-complexes that contain 6, 10 and 6 different IFT particle proteins, respectively 25, 30, 31, 46, 47.”

What the sources say

• Supported

  The IFT-A architecture section identifies six IFT-A proteins. The IFT-B core (IFT-B1) section identifies six original members and four added members, totaling ten; the peripheral IFT-B (IFT-B2) section identifies six subunits and names the two IFT-B subcomplexes. (LLM, conf=0.94)

  cites [25] Taschner, M. & Lorentzen, E. The intraflagellar transport machinery. Cold Spring Harb. Perspect. Biol. 8, a028092 (2016). source
• ?Not checked — no full text of the sourcecites [30] Pedersen, L. B. & Rosenbaum, J. L. Intraflagellar transport (IFT) role in ciliary assembly, resorption and signalling. Curr. Top. Dev. Biol. 85, 23–61 (2008). source
• Supported

  The IFT trains—Composition section states that IFT-A contains six subunits and that IFT-B is further organized into IFT-B1 with ten subunits and IFT-B2 with six. This directly supports the attributed counts. (LLM, conf=0.95)

  cites [31] Prevo, B., Scholey, J. M. & Peterman, E. J. G. Intraflagellar transport: mechanisms of motor action, cooperation, and cargo delivery. FEBS J. 284, 2905–2931 (2017). source

In the paper

“A large number of studies in different organisms subsequently confirmed a universal requirement for these motors in IFT, but also demonstrated that some organisms additionally use ‘accessory’ kinesins to regulate certain aspects of ciliary assembly or function 23, 39.”

What the sources say

• Partly supported

  The “Intraflagellar transport” section (page not available) describes kinesin-2 and dynein 2 as IFT motors, but says mutations in their subunits usually cause severe ciliary defects in most organisms studied—not that their requirement is universal. The “Role of kinesin-2 motors in axoneme extension” section (page not available) describes additional kinesin-2 motors with overlapping or partially redundant roles in some organisms, supporting the accessory-motor part of the claim. (LLM, conf=0.87)

  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). sourceExperimental — accuracy not yet measured
• Partly supported

  The Intraflagellar transport section (page unavailable) says heterotrimeric kinesin-2 is critical for anterograde IFT in every organism tested and identifies cytoplasmic dynein as the retrograde IFT motor. The IFT kinesins section (page unavailable) describes accessory kinesins with cell-specific roles in ciliary shape and function. The copy does not establish the claimed universal requirement for cytoplasmic dynein across organisms. (LLM, conf=0.84)

  cites [39] Verhey, K. J., Dishinger, J. & Kee, H. L. Kinesin motors and primary cilia. Biochem. Soc. Trans. 39, 1120–1125 (2011). sourceExperimental — accuracy not yet measured

In the paper

“The BBSome proteins were initially thought to facilitate the delivery of GPCRs to cilia 73–75; however, it has been proposed that BBSome proteins primarily regulate ciliary export of signalling proteins 72, 76, 77, 78.”

What the sources say

• Supported

  The section ‘The BBSome is required for the export of specific proteins from the flagellum’ proposes that the BBSome continually removes certain proteins from flagella. The discussion of proteins accumulated in BBS mutants identifies several as potentially involved in signaling. The paper also describes the earlier interpretation that the BBSome helps transport some membrane proteins into cilia. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  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). source
• Partly supported

  The Discussion (page unavailable) proposes that BBSome-mediated export may apply to many cycling membrane-associated proteins, supporting the cited export proposal. It does not establish that export is the BBSome’s primary role across signalling proteins; the Introduction says both import and export of ciliary GPCRs may be affected. (LLM, conf=0.82)

  cites [76] Lechtreck, K. F. et al. Cycling of the signaling protein phospholipase D through cilia requires the BBSome only for the export phase. J. Cell Biol. 201, 249–261 (2013). sourceExperimental — accuracy not yet measured
• Supported

  In “What is the trafficking step mediated by the BBSome?” (page not provided), the paper describes earlier evidence for a role in GPCR entry, then proposes a model limiting BBSome function to ciliary exit. It also reports evidence for BBSome-dependent exit of several signaling receptors. (LLM, conf=0.93)

  cites [77] Nachury, M. V. The molecular machines that traffic signaling receptors into and out of cilia. Curr. Opin. Cell Biol. 51, 124–131 (2018). source
• Supported

  The “Cell Biology of the BBSome” section says the BBSome was initially thought to traffic GPCRs into cilia, then describes evidence that it removes GPCRs from cilia. The section concludes that the BBSome promotes protein export from cilia; the discussion of retrograde transport also identifies signaling proteins as affected cargoes. Page numbers are not available in the supplied passages. (LLM, conf=0.94)

  cites [78] Wingfield, J. L., Lechtreck, K.-F. & Lorentzen, E. Trafficking of ciliary membrane proteins by the intraflagellar transport/BBSome machinery. Essays Biochem. 62, 753–763 (2018). source

In the paper

“Likewise, progress has been made towards understanding the interactions between specific IFT particle polypeptides and specific ciliary cargo proteins or motor subunits during anterograde or retrograde IFT, as well as how IFT motor activity is regulated 24, 48–52.”

What the sources say

• Partly supported

  The sections on cargo binding and known IFT binding sites describe specific interactions, including IFT81/IFT74 with tubulin and IFT46 with an adaptor for outer dynein arms. The building-blocks section identifies the motors for anterograde and retrograde transport, but the paper does not substantively explain how IFT motor activity is regulated or establish the claimed interactions with specific motor subunits. Page numbers were unavailable in our copy. (LLM, conf=0.82)

  cites [24] Lechtreck, K. F. IFT-cargo interactions and protein transport in cilia. Trends Biochem. Sci. 40, 765–778 (2015). sourceExperimental — accuracy not yet measured
• Supported

  The Review sections on IFT complex–cargo and complex–motor interactions describe evidence linking named IFT proteins to ciliary cargoes and motor subunits. They also discuss coordination of anterograde motors and possible mechanisms regulating motor activity. The review emphasizes that many direct interactions and regulatory details remain unresolved, consistent with the claim’s wording that progress has been made toward understanding them. (LLM, conf=0.88)

  cites [48] Bhogaraju, S., Engel, B. D. & Lorentzen, E. Intraflagellar transport complex structure and cargo interactions. Cilia 2, 10 (2013). sourceExperimental — accuracy not yet measured
• Supported

  This paper supports the motor-regulation part of the multiply cited sentence. The Discussion reports that dynein-2 dimerization inhibits motor activity and that disrupting the inhibitory arrangement restores ATPase activity and motility. The citation need not support the separate claim about specific IFT-particle interactions. (LLM, conf=0.91)

  cites [49] Toropova, K., Mladenov, M. & Roberts, A. J. Intraflagellar transport dynein is autoinhibited by trapping of its mechanical and track-binding elements. Nat. Struct. Mol. Biol. 24, 461–468 (2017). sourceExperimental — accuracy not yet measured
• Supported

  The Discussion (page not provided) reports that this study identified an interaction between the kinesin-II motor and a tetramer of specific IFT-B subunits. That directly supports the interaction aspect of the broadly cited statement about progress in understanding IFT. (LLM, conf=0.90)

  cites [50] Funabashi, T., Katoh, Y., Okazaki, M., Sugawa, M. & Nakayama, K. Interaction of heterotrimeric kinesin-II with IFT-B-connecting tetramer is crucial for ciliogenesis. J. Cell Biol. 217, 2867–2876 (2018). sourceExperimental — accuracy not yet measured
• Supported

  The Abstract and “Building the first IFT-kinesin-2 complex” section describe how a specific IFT-B subunit recruits the OSM-3 motor and how incorporation into the complex activates it in C. elegans sensory cilia. This supports the motor-interaction and regulation portion of the multiply cited sentence; the paper is not being relied on here for its cargo-protein or retrograde-transport examples. (LLM, conf=0.90)

  cites [51] Mohamed, M. A. A., Stepp, W. L. & Okten, Z. Reconstitution reveals motor activation for intraflagellar transport. Nature 557, 387–391 (2018). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results and Discussion report that FLA8/KIF3B phosphorylation regulates IFT entry and that phosphatase knockdown reduces anterograde and retrograde IFT velocities. The paper also discusses kinesin-II interaction with IFT-B, but our copy does not establish specific IFT-particle-polypeptide interactions with ciliary cargo proteins or retrograde motor subunits. No page number is available in our copy. (LLM, conf=0.82)

  cites [52] Liang, Y., Zhu, X., Wu, Q. & Pan, J. Ciliary length sensing regulates IFT entry via changes in FLA8/KIF3B phosphorylation to control ciliary assembly. Curr. Biol. 28, 2429–2435 (2018). sourceExperimental — accuracy not yet measured

In the paper

“In addition to canonical pathways, HH signalling can occur though so-called non-canonical pathways, which involve either GLI-independent mechanisms or SMO-independent regulation of GLI activity 106, 107.”

What the sources say

• ?Not checked — no full text of the sourcecites [106] Bitgood, M. J. & McMahon, A. P. Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo. Dev. Biol. 172, 126–138 (1995). source
• Partly supported

  The “Non-canonical Shh signaling” section and Fig. 2 describe GLI-independent mechanisms, including a SMO-independent type. They do not describe SMO-independent regulation of GLI activity; their SMO-independent example is also GLI-independent. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  cites [107] Carballo, G. B., Honorato, J. R., de Lopes, G. P. F. & Spohr, T. C. L. S. E. A highlight on Sonic hedgehog pathway. Cell Commun. Signal. 16, 11 (2018). sourceExperimental — accuracy not yet measured

In the paper

“Interestingly, the extracellular domains also have an interface that accommodates cholesterol derivatives, and binding of PTCH1 to the N-fragment of SHH potentially limits access to or exit of these derivatives from this site.”

What the sources say

• ?Could not verify

  The Introduction (page unavailable) says that SHH binds PTCH1, but it does not describe PTCH1’s extracellular structure or a cholesterol-derivative binding site. Searches for the proposed interface and for cholesterol or sterol access found no passage addressing whether SHH binding limits entry to or exit from such a site. (LLM, conf=0.74)

  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

In the paper

“The two extracellular domains of PTCH1 interact with SHH, although the two structural studies that investigated SHH binding identified different interacting interfaces with native lipidated SHH and an SHH N-fragment 111, 112.”

What the sources say

• Partly supported

  The Introduction (page unavailable) says that Hedgehog proteins, including SHH, bind PTCH1. It does not describe PTCH1’s two extracellular domains or compare binding interfaces identified by structural studies using lipidated SHH and an SHH N-fragment. (LLM, conf=0.86)

  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

In the paper

“First, PTCH1 shows similarity to members of the resistance-nodulation-cell division (RND) family of bacterial efflux transporters and to sterol sensing domains in the cholesterol trafficking protein, Niemann-Pick C1 (NPC1).”

What the sources say

• ?Could not verify

  The Introduction describes PTCH1 as a 12-transmembrane Hedgehog receptor, but does not discuss its structural similarity to other proteins. Searches for RND bacterial efflux transporters and NPC1 sterol-sensing domains found no passage addressing either comparison in our copy; page numbers were not available. (LLM, conf=0.74)

  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

In the paper

“The intermediate steps between SMO activation, GLIA formation and translocation to the nucleus are not well understood, although GLI2 and GLI3 proteins accumulate in cilia tips upon HH pathway activation, suggesting that GLIA formation is regulated in the vicinity of cilia 117.”

What the sources say

• Supported

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

  cites [117] Dorn, K. V., Hughes, C. E. & Rohatgi, R. A. Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia. Dev. Cell 23, 823–835 (2012). source

In the paper

“Binding of PTCH1 to the N-fragment of SHH is enhanced by cholesterol derivatives and it is predicted that binding of cholesterol to the extracellular domain interface might arise from cholesterol transport by PTCH1 111.”

What the sources say

• Partly supported

  The Introduction (page unavailable) says that Hedgehog proteins, including SHH, bind PTCH1. It does not specify the SHH N-fragment, say that cholesterol derivatives enhance binding, or predict cholesterol binding at an extracellular-domain interface through PTCH1 transport. Searches for those cholesterol-related claims found no supporting passage. (LLM, conf=0.83)

  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

In the paper

“The transmembrane segments 2–6 in PTCH1 constitute the sterol-sensing domain, and are sufficient to accommodate cholesterol derivatives 111, 112.”

What the sources say

• ?Could not verify

  The Introduction describes PTCH1 as a 12-transmembrane receptor, but does not identify segments 2–6 as a sterol-sensing domain or say they accommodate cholesterol derivatives. Searches for those terms in our copy found no passage addressing the claimed structure or binding capacity; the Results instead concern Smoothened signaling outside primary cilia. Page numbers were not available in the indexed copy. (LLM, conf=0.75)

  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

In the paper

“Furthermore, the 7-transmembrane receptor GPR175 (also known as TPRA1 or TPRA40) is enriched in cilia in the presence of SHH, and might regulate maximal activation of pathways downstream of SMO by coupling to the inhibitory Gα protein, Gαi, leading to decreased cAMP levels and inhibiting PKA-mediated formation of GLI3R 116.”

What the sources say

• ?Could not verify

  The Abstract and ‘Redistribution of membrane cholesterol by PTCH1’ section discuss SHH, PTCH1, and SMO regulation, but do not address GPR175. Searches for GPR175/TPRA1/TPRA40 and Gαi/cAMP/PKA/GLI3R found no passage supporting the claimed ciliary enrichment or signaling mechanism. (LLM, conf=0.76)

  cites [116] Zhang, Y. et al. Structural basis for cholesterol transport-like activity of the hedgehog receptor Patched. Cell 175, 1352–1364 (2018). sourceExperimental — accuracy not yet measured

In the paper

“CAV1 localizes to the base of cilia in cultured mammalian cells in a manner dependent on the kinesin-3 motor protein KIF13B; both CAV1 and KIF13B have been implicated in the regulation of SHH signalling 99.”

What the sources say

• Partly supported

  The Results section on Ptch1 accumulation in lipid rafts reports that Shh treatment increases Ptch1 colocalization with Cav-1, and the Discussion links Cav-1-positive lipid rafts to Shh-related Ptch1 trafficking. Our copy does not establish that Cav-1 localizes to the ciliary base, that its localization depends on KIF13B, or that KIF13B regulates SHH signalling (searched: KIF13B and Caveolin-1 ciliary base). The supplied passages have no page numbers. (LLM, conf=0.78)

  cites [99] Yue, S. et al. Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception. eLife 3, e02555 (2014). sourceExperimental — accuracy not yet measured

In the paper

“Binding of SHH to its 12-transmembrane receptor Patched-1 (PTCH1) triggers endocytic clearance of PTCH1 from the cilium in a process that relies on ubiquitination of the receptor by the HECT domain E3 ubiquitin ligases SMURF1 and SMURF2, which co-localize with PTCH1 in caveolin-1 (CAV1)-positive lipid rafts and vesicles 98.”

What the sources say

• Partly supported

  In “Enrichment of Hh pathway components in cilia” (page unavailable), the paper says Ptch1 is the Hh receptor and exits the cilium upon exposure to ligand. It does not describe that exit as endocytic clearance or attribute it to SMURF1/SMURF2-mediated ubiquitination or co-localization in CAV1-positive lipid rafts and vesicles. (LLM, conf=0.90)

  cites [98] Goetz, S. C. & Anderson, K. V. The primary cilium: a signalling centre during vertebrate development. Nat. Rev. Genet. 11, 331–344 (2010). sourceExperimental — accuracy not yet measured

In the paper

“Interestingly, a longitudinal tunnel capable of accommodating cholesterol was identified in the transmembrane region of active SMO, suggesting that SMO itself might move cholesterol from the plasma membrane to the extracellular domain 113.”

What the sources say

• ?Could not verify

  The passage describing a hydrophobic pocket (section labeled Abstract; page unavailable) locates it in Ptch1, not active SMO. A further passage says the mechanism of SMO inhibition remains poorly understood. Searches for a longitudinal tunnel in SMO and cholesterol movement through SMO found no passage addressing either claim in our copy. (LLM, conf=0.78)

  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

“Oxysterols can also bind to the cysteine rich domain and activate SMO downstream and independent of PTCH1 removal from cilia 102, 114; however, the physiological role of oxysterols in HH pathway activation is not clear.”

What the sources say

• ?Not checked — no full text of the sourcecites [102] Corbit, K. C. et al. Vertebrate Smoothened functions at the primary cilium. Nature 437, 1018–1021 (2005). source
• Partly supported

  The Results section, “Allosteric activation of the 7TM domain by sterol-bound CRD” (page unavailable), reports that 20(S)-hydroxycholesterol activates SMO and that oxysterol-bound CRD allosterically activates its 7TM domain. The paper does not establish that this occurs independently of PTCH1 removal from cilia, nor does it specifically state that oxysterols’ physiological role in HH activation is unclear. (LLM, conf=0.85)

  cites [114] Huang, P. et al. Structural basis of Smoothened activation in Hedgehog signaling. Cell 174, 312–324 (2018). sourceExperimental — accuracy not yet measured

In the paper

“CAV1 has also been reported to have ciliary functions in C. elegans 100.”

What the sources say

• Partly supported

  The Results section on KIF13B and NPHP4 reports CAV1 at the ciliary transition zone in RPE1 cells, supporting a ciliary role for CAV1. The paper’s C. elegans passages instead discuss KLP-6 and polycystin-2; they do not report a ciliary function for CAV1 in that species. No page numbers are available in our copy. (LLM, conf=0.86)

  cites [100] Schou, K. B. et al. KIF13B establishes a CAV1-enriched microdomain at the ciliary transition zone to promote Sonic hedgehog signalling. Nat. Commun. 8, 14177 (2017). sourceExperimental — accuracy not yet measured

In the paper

“Removal of ciliary PTCH1 in response to SHH binding is associated with ciliary enrichment of Smoothened (SMO) 101, 102 –a 7-transmembrane receptor belonging to the class F (frizzled) family of GPCRs – which ultimately leads to the formation of GLIA, predominantly by phosphorylation of GLI2 103 (Figure 2).”

What the sources say

• Partly supported

  The Introduction states that Shh activation causes Ptch1 to leave the cilium as Smo enters it, supporting the trafficking portion of the claim. Our copy does not identify Smo as a class F frizzled GPCR or describe GLIA formation through GLI2 phosphorylation; the printed sentence places a separate citation after that downstream claim. (LLM, conf=0.87)

  cites [101] Scheidel, N., Kennedy, J. & Blacque, O. E. Endosome maturation factors Rabenosyn-5/VPS45 and caveolin-1 regulate ciliary membrane and polycystin-2 homeostasis. EMBO J. 37, e98248 (2018). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [102] Corbit, K. C. et al. Vertebrate Smoothened functions at the primary cilium. Nature 437, 1018–1021 (2005). source
• ?Not checked — no full text of the sourcecites [103] Rohatgi, R., Milenkovic, L. & Scott, M. P. Patched1 regulates hedgehog signaling at the primary cilium. Science 317, 372–376 (2007). source

In the paper

“Importantly, the absence of GPR161, PKA, and SUFU induces high levels of SHH signalling during mouse neural tube development 122, 125, 126, similar to the effect of Ptch1 deletion, which induces activation of SMO signalling 127.”

What the sources say

• ?Could not verify

  Our copy discusses PKA-dependent Gli3 processing in the Hedgehog pathway (Abstract; Figure 1 caption), but does not report that loss of PKA, GPR161, or SUFU causes high SHH signalling in the developing mouse neural tube. Searches for neural-tube signalling and the named proteins also found no passage supporting the comparison with Ptch1 deletion and SMO activation. (LLM, conf=0.76)

  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
• Partly supported

  The introduction (page unavailable) says that genetic inactivation of Sufu constitutively activates Hedgehog target genes in mice, supporting the SUFU portion of the claim. The paper does not establish this specifically during mouse neural tube development, and its PKA experiments manipulate activity in cultured cells rather than test PKA absence in the neural tube. The Ptch1 comparison has a separate citation in the citing sentence. (LLM, conf=0.86)

  cites [125] Humke, E. W., Dorn, K. V., Milenkovic, L., Scott, M. P. & Rohatgi, R. The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins. Genes Dev. 24, 670–682 (2010). sourceExperimental — accuracy not yet measured
• Supported

  The Results and Discussion report widespread ventral-marker expression in Sufu-mutant E9.5 spinal cords and broad expression of the Hedgehog target genes Gli1 and Ptch1 in Sufu-mutant embryos. This supports the SUFU-loss portion of the claim; the sentence assigns the Ptch1-deletion comparison to a separate citation. (LLM, conf=0.91)

  cites [126] Jia, J. et al. Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia. Dev. Biol. 330, 452–460 (2009). source

In the paper

“KIF7, also becomes enriched in ciliary tips during activation of HH signalling 136, 137, where it. functions as both a positive and negative regulator of SHH signalling by modifying ciliary architecture 136, 137.”

What the sources say

• ?Could not verify

  The Introduction (page unavailable) discusses ciliary Hedgehog signalling and describes Smoothened enrichment in cilia, but does not make the claimed point about KIF7. Searches for KIF7, ciliary-tip enrichment, and its proposed positive and negative effects through ciliary architecture found no passage addressing those claims. (LLM, conf=0.76)

  cites [136] Hwang, S. H. et al. The G protein-coupled receptor Gpr161 regulates forelimb formation, limb patterning and skeletal morphogenesis in a primary cilium-dependent manner. Development 145, dev154054 (2018). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Introduction discusses cilium-dependent activation and repression of SHH signalling, but does not attribute either role to KIF7. Searches for KIF7, its enrichment at ciliary tips, and its effect on ciliary architecture found no passage addressing those claims; the Discussion instead mentions Kif3a and Gpr161. Page numbers were not available in our copy. (LLM, conf=0.77)

  cites [137] Shimada, I. S. et al. Basal suppression of the Sonic Hedgehog pathway by the G-protein-coupled receptor Gpr161 restricts medulloblastoma pathogenesis. Cell Rep. 22, 1169–1184 (2018). sourceExperimental — accuracy not yet measured

In the paper

“However, the neural tube ventralization phenotypes of Tulp3 and IFT-A mutants, and Gpr161 mutants are weaker than those resulting from mutations in downstream negative regulators of HH signalling such as Sufu and PKA 132, suggesting the existence of additional inputs into PKA activation other than GPR161 133.”

What the sources say

• ?Not checked — no full text of the sourcecites [132] Qin, J., Lin, Y., Norman, R. X., Ko, H. W. & Eggenschwiler, J. T. Intraflagellar transport protein 122 antagonizes Sonic Hedgehog signaling and controls ciliary localization of pathway components. Proc. Natl Acad. Sci. USA 108, 1456–1461 (2011). source
• Partly supported

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

  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

“The importance of HH pathway repression is illustrated by the finding that premature SHH signalling resulting from disruption of GPR161 causes defects in limb and skeletal morphogenesis 134, cerebellar granule cell hyper-proliferation and formation of SHH-subtype medulloblastoma 135.”

What the sources say

• ?Not checked — no full text of the sourcecites [134] Hwang, S. H. & Mukhopadhyay, S. G-Protein-coupled receptors and localized signaling in the primary cilium during ventral neural tube patterning. Birth Defects Res. A Clin. Mol. Teratol 103, 12–19 (2015). source
• Partly supported

  The Results section on GPR161 in neural progenitor cells (page unavailable) reports that GPR161 loss increases Hedgehog signalling and alters neural progenitor specification. The Introduction mentions limb-bud patterning by Hedgehog ligands, but our copy does not link GPR161 disruption to limb or skeletal defects. The cerebellar proliferation and medulloblastoma findings carry a separate citation (135), so they are not attributed to this source. (LLM, conf=0.82)

  cites [135] Pusapati, G. V. et al. G protein-coupled receptors control the sensitivity of cells to the morphogen Sonic Hedgehog. Sci. Signal. 11, eaao5749 (2018). sourceExperimental — accuracy not yet measured

In the paper

“activation of GPBAR1 on ciliated cells induced co-localization of GPBAR1 with Gαi, decreased cAMP signalling, activated ERK signalling, and decreased cellular proliferation.”

What the sources say

• Partly supported

  The Introduction (page unavailable) reports that TGR5 ligand treatment in ciliated cholangiocytes decreased cAMP levels and proliferation while activating ERK signaling. The paper identifies TGR5 as GPBAR1, but the passages do not report that activation induced co-localization with Gαi. (LLM, conf=0.87)

  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

“Activation of PKA in different subcellular regions is mediated by local cAMP production and anchoring of PKA to A-kinase anchoring proteins (AKAPs) 141.”

What the sources say

• ?Could not verify

  The Results section on distinct ciliary compartments describes the localization of PI(4)P and PI(4,5)P2, not PKA activation. Searches of our full-text copy for PKA, cAMP, AKAP, and the proposed mechanism found no passage addressing local cAMP production or PKA anchoring. The copy provides neither support for nor a contradiction of the claim. (LLM, conf=0.76)

  cites [141] Garcia-Gonzalo, F. R. et al. Phosphoinositides regulate ciliary protein trafficking to modulate Hedgehog signaling. Dev. Cell 34, 400–409 (2015). sourceExperimental — accuracy not yet measured

In the paper

“Upon activation, ciliary V2R seems to activate adenylyl cyclase, which increases local cAMP concentrations and activates a cation-selective channel to regulate intraciliary Ca+2 signals 162.”

What the sources say

• ?Could not verify

  The Results and Discussion describe ciliary calcium signaling through dopamine receptor DR5 and the CaV1.2 channel, not through V2R. Searches for V2R, vasopressin, adenylyl cyclase, and the proposed cAMP-dependent channel pathway found no passage addressing that mechanism in our copy. No page numbers are available for these passages. (LLM, conf=0.75)

  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

“Activation of GPBAR1 on non-ciliated cholangiocytes induced co-localization of GPBAR1 with Gαs, increased cAMP signalling, inhibited ERK signalling, and increased cellular proliferation 155”

What the sources say

• Partly supported

  The Introduction (page unavailable) reports that TGR5 ligands increased cAMP levels and proliferation and inhibited ERK signaling in non-ciliated cholangiocytes. It does not report that activation induced co-localization of GPBAR1 (TGR5) with Gαs, so that part of the claim is unsupported. (LLM, conf=0.88)

  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

“cholangiocyte cilia are enriched for two different GPCRs — purinergic receptor P2Y12 (P2RY12) 155 and G-protein coupled bile acid receptor 1 (GPBAR1, also known as TGR5) 157, 158, as well as the cAMP signalling proteins adenylyl cyclase, PKA, exchange protein directly activated by cAMP isoform 2 (EPAC2), and A-kinase anchoring protein (AKAP150) 155”

What the sources say

• Partly supported

  The Introduction (page unavailable) says TGR5 is enriched in cholangiocyte cilia. It discusses adenylyl cyclase in neuronal cilia and PKA in other signaling contexts, but does not establish enrichment of P2RY12, adenylyl cyclase, PKA, EPAC2, or AKAP150 in cholangiocyte cilia (searched P2Y12, EPAC2, and AKAP150). (LLM, conf=0.88)

  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
• Supported

  The paper’s summary reports P2Y12, adenylyl cyclases, PKA, EPAC2, and AKAP150 in cholangiocyte cilia; the cAMP-signaling results describe their ciliary localization in more detail. GPBAR1/TGR5 has separate citations in the citing sentence and is not attributed to this paper. (LLM, conf=0.91)

  cites [157] Masyuk, A. I. et al. Cholangiocyte primary cilia are chemosensory organelles that detect biliary nucleotides via P2Y12 purinergic receptors. Am. J. Physiol. Gastrointest. Liver Physiol. 295, G725–G734 (2008). source
• Supported

  The citations attached to P2RY12 and the listed cAMP-signalling proteins are separate; this source is cited for GPBAR1/TGR5. The Abstract states that TGR5 is localized to cholangiocyte primary cilia, and the Conclusion identifies GPBAR1 as the gene encoding TGR5. (LLM, conf=0.93)

  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

“Another negative regulator of SHH signalling, Suppressor of FUSED (SUFU) restrains GLI3 in the cytoplasm and promotes GLI3R processing 123 in a cilia-independent step 124.”

What the sources say

• ?Could not verify

  The Results describe formation of the Gli3-83 repressor and suggest that Gli3 processing may depend on PKA activity. Searches for SUFU, cytoplasmic restraint, and a cilia-independent step found no passage in our copy addressing SUFU’s proposed role or the cilia qualifier. (LLM, conf=0.76)

  cites [123] Wang, B., Fallon, J. F. & Beachy, P. A. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb. Cell 100, 423–434 (2000). sourceExperimental — accuracy not yet measured
• Supported

  Citation 124 is attached to the cilia-independent aspect of SUFU’s negative regulation. The Results state that SUFU negatively regulates mammalian SHH signalling independently of cilia, and the Discussion says primary cilia are not required for SUFU to inhibit GLI activity. Page numbers are unavailable in our copy. (LLM, conf=0.91)

  cites [124] Mukhopadhyay, S. et al. The ciliary G-protein-coupled receptor Gpr161 negatively regulates the Sonic hedgehog pathway via cAMP signaling. Cell 152, 210–223 (2013). source

In the paper

“nephrocystin-2 (NPHP2, also known as inversin, which when overexpressed inhibits DVL1-mediated activation of WNT reporter constructs in mammalian cells and rescues secondary axis formation induced by overexpression of Dsh or CK1μ in Xenopus laevis 198.”

What the sources say

• ?Could not verify

  The passages on Wnt signaling and BBS10/BBS12 knockdown in differentiating preadipocytes do not address NPHP2/inversin overexpression. Searches for DVL1-mediated WNT reporter activation and secondary-axis formation in Xenopus found no passage addressing those experiments. Section and page labels were unavailable in our copy. (LLM, conf=0.77)

  cites [198] Marion, V. et al. Transient ciliogenesis involving Bardet-Biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation. Proc. Natl Acad. Sci. USA 106, 1820–1825 (2009). sourceExperimental — accuracy not yet measured

In the paper

“NPY also has an important role in the central regulation of food intake and energy expenditure 181.”

What the sources say

• ?Could not verify

  The Main Text (page unavailable) discusses MC4R-expressing neurons, their ligands αMSH and AGRP, and regulation of feeding and energy homeostasis. Searches for “NPY” and “neuropeptide Y” found no passage in our copy addressing NPY’s role in food intake or energy expenditure. (LLM, conf=0.76)

  cites [181] Siljee, J. E. et al. Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity. Nat. Genet. 50, 180–185 (2018). sourceExperimental — accuracy not yet measured

In the paper

“activated NPY2R accumulates at the ciliary tip and is released in extracellular vesicles called ectosomes 28”

What the sources say

• Supported

  The Discussion section, “Receptor packaging into ectosomes at the tips of cilia,” says NPY2R concentrates at the ciliary tip before being packaged into buds for ectocytosis. The Results section, “Ectocytosis is not limited to pathological or artificial settings,” reports that activating NPY2R with an agonist led to its ectocytosis. Page numbers are not provided in our copy. (LLM, conf=0.95)

  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

“deletion of BBS proteins leads to failure of somatostatin receptor subtype 3 (SSTR3), melanin-concentrating hormone receptor 1 and neuropeptide Y (NPY) receptor subtype 2 (NPY2R) to localize to neuronal cilia, whereas, dopamine receptor 1 accumulates in neuronal cilia 73, 74, 168.”

What the sources say

• Partly supported

  The paper’s opening summary and Results report that neurons from Bbs2- or Bbs4-null mice lack ciliary Sstr3 and Mchr1. Our copy does not report NPY2R failing to localize or dopamine receptor 1 accumulating in neuronal cilia; searches for those receptors found no supporting passage. Page numbers were not available. (LLM, conf=0.88)

  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). sourceExperimental — accuracy not yet measured
• ?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

“morpholino-induced depletion of NPHP2 in X. laevis and zebrafish disrupted convergent extension — a process that was rescued by overexpression of mouse NPHP2 or Diversin, respectively 198.”

What the sources say

• ?Could not verify

  The section “BBS10 and BBS12 Affect Ciliogenesis and Adipogenic Pathways” (page not provided) describes RNAi knockdown in human preadipocytes, not NPHP2 morpholino depletion in Xenopus or zebrafish. Searches for NPHP2, Diversin, convergent extension, and the claimed rescue found no passage addressing those experiments in our copy. (LLM, conf=0.76)

  cites [198] Marion, V. et al. Transient ciliogenesis involving Bardet-Biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation. Proc. Natl Acad. Sci. USA 106, 1820–1825 (2009). sourceExperimental — accuracy not yet measured

In the paper

“depletion of the gene that encodes the ciliary TZ NPHP module component, RPGRIP1L, in mouse embryos leads to ventricular septal defects associated with loss of localization, which display cardiac ventricular septal defects 254 is associated with loss of localization of PDGFRα to primary cilia and reduced expression of the PDGFRα target gene, Hifα, in cardiac ventricular tissue 243.”

What the sources say

• Partly supported

  The Results (Fig. 2B–H; page not available) report loss of ciliary PDGFRα localization in Ift20-deficient cranial osteoblasts. They do not report RPGRIP1L depletion, ventricular septal defects, or reduced Hifα expression in cardiac ventricular tissue; searches for those terms found no supporting passage. (LLM, conf=0.84)

  cites [243] Noda, K., Kitami, M., Kitami, K., Kaku, M. & Komatsu, Y. Canonical and noncanonical intraflagellar transport regulates craniofacial skeletal development. Proc. Natl Acad. Sci. USA 113, E2589–E2597 (2016). sourceExperimental — accuracy not yet measured

In the paper

“although IGF-IR is localized and activated at the plasma membrane, adipocyte differentiation, which is associated with transient ciliogenesis 197, 230, requires activation of IGF-IR in the primary cilium in cultures of 3T3-L1 preadipocytes 230”

What the sources say

• ?Could not verify

  The Results section on transient FGF signaling describes FGF2-induced ciliary elongation in NIH3T3 fibroblasts, not IGF-IR activation in 3T3-L1 preadipocytes. Searches for IGF-IR, adipocyte differentiation, and transient ciliogenesis found no passage in our copy addressing the attributed claim; page numbers were unavailable. (LLM, conf=0.76)

  cites [230] Kunova Bosakova, M. et al. Regulation of ciliary function by fibroblast growth factor signaling identifies FGFR3-related disorders achondroplasia and thanatophoric dysplasia as ciliopathies. Hum. Mol. Genet. 27, 1093–1105 (2018). sourceExperimental — accuracy not yet measured

In the paper

“PDGFRα is principally localized to primary cilia 225, 240–243, although non-ciliary localizations for this isoform have been reported for specific cell types 243–245.”

What the sources say

• ?Could not verify

  The Results and Discussion passages (page not provided) describe EGFR and PKD2 in primary cilia, not PDGFRα. Searches for PDGFRα and non-ciliary localization yielded no passage addressing either part of the claim. (LLM, conf=0.78)

  cites [225] Ma, R. et al. PKD2 functions as an epidermal growth factor-activated plasma membrane channel. Mol. Cell. Biol. 25, 8285–8298 (2005). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [240] Heldin, C.-H., Lennartsson, J. & Westermark, B. Involvement of platelet-derived growth factor ligands and receptors in tumorigenesis. J. Intern. Med. 283, 16–44 (2018). source
• Supported

  The Results and Discussion report that PDGFRα localizes predominantly to primary cilia in NIH3T3 fibroblasts. The same section reports that most PDGFRα in quiescent wild-type mouse embryonic fibroblasts is ciliary, while a low level is present at the cell surface. These findings support the claim for the fibroblast cell types studied. (LLM, conf=0.90)

  cites [241] Schneider, L. et al. PDGFRαα signaling is regulated through the primary cilium in fibroblasts. Curr. Biol. 15, 1861–1866 (2005). source
• ?Not matched

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

  cites [242] Vestergaard, M. L., Awan, A., Warzecha, C. B., Christensen, S. T. & Andersen, C. Y. in Human Embryonic Stem Cell Protocols (ed. Turksen, K.) 123–140 (Springer, NY, 2016).
• Partly supported

  The Results (page unavailable) show PDGFRα on primary cilia in control osteoblasts and on the cell surface of Ift20-mutant osteoblasts lacking cilia. This supports ciliary localization and a non-ciliary example, but the paper does not establish that PDGFRα is principally ciliary across cell types. (LLM, conf=0.82)

  cites [243] Noda, K., Kitami, M., Kitami, K., Kaku, M. & Komatsu, Y. Canonical and noncanonical intraflagellar transport regulates craniofacial skeletal development. Proc. Natl Acad. Sci. USA 113, E2589–E2597 (2016). sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction says PDGFRα localizes to cilia, and the Results report it along ventricular cilia in E11.5 mouse hearts (page numbers unavailable). The paper does not establish that its localization is principally ciliary or report non-ciliary localization in specific cell types; failure to detect it at atrial cilia does not establish where it is instead. (LLM, conf=0.86)

  cites [244] Gerhardt, C., Lier, J. M., Kuschel, S. & Rüther, U. The ciliary protein Ftm is required for ventricular wall and septal development. PLOS ONE 8, e57545 (2013). sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Results section, “FAPs are dynamically ciliated during muscle regeneration” (page unavailable), says that PDGFRα-expressing FAPs are frequently ciliated. That describes the cells, not where PDGFRα itself is located. Searches for ciliary and non-ciliary PDGFRα localization found no passage addressing either part of the claim. (LLM, conf=0.75)

  cites [245] Kopinke, D., Roberson, E. C. & Reiter, J. F. Ciliary Hedgehog signaling restricts injury-induced adipogenesis. Cell 170, 340–351 (2017). sourceExperimental — accuracy not yet measured

In the paper

“depletion of BBS4 in cultured cells (which results in both canonical and WNT–PCP defects in zebrafish) reduces proteasomal activity and leads to an accumulation of cytoplasmic and nuclear β-catenin 216”

What the sources say

• Partly supported

  The Discussion reports that Bbs4 is essential for proteasomal degradation or processing, supporting the proteasomal part of the claim. The Results report increased phosphorylated β-catenin at the ciliary base after Rpgrip1l loss, not cytoplasmic and nuclear β-catenin accumulation after BBS4 depletion. The cited passages also do not establish the parenthetical zebrafish defects. (LLM, conf=0.85)

  cites [216] Gerhardt, C. et al. The transition zone protein Rpgrip1l regulates proteasomal activity at the primary cilium. J. Cell Biol. 210, 1027 (2015). sourceExperimental — accuracy not yet measured

In the paper

“demonstrating that primary cilia are redundant for both branches of WNT signalling 203.”

What the sources say

• Partly supported

  The Discussion (page unavailable) reports that studies suggest cilia have no role in Wnt signalling during early development. That narrower, hedged statement does not establish that primary cilia are redundant for both branches of WNT signalling across contexts; the same passage says their role has not been clearly defined. (LLM, conf=0.85)

  cites [203] Vuong, L. T., Mukhopadhyay, B. & Choi, K.-W. Kinesin-II recruits Armadillo and Dishevelled for Wingless signaling in Drosophila. Development 141, 3222–3232 (2014). sourceExperimental — accuracy not yet measured

In the paper

“These defects in glucose handling are linked to defects in insulin-mediated activation of the PI3K–AKT pathway in β-cells, which relies on ciliary recruitment of activated IR subtype A (IR-A), which controls the production of insulin in these cells 235, 238.”

What the sources say

• ?Not checked — no full text of the sourcecites [235] Wang, H. et al. Hsp90α forms a stable complex at the cilium neck for the interaction of signalling molecules in IGF-1 receptor signalling. J. Cell Sci. 128, 100–108 (2015). source
• ?Could not verify

  The section 'Cilia-Related Signaling in the Control of Glucose Metabolism' discusses cilia-dependent glucose uptake through SMO and AMPK in fibroblasts, muscle, and brown adipocytes. Searches for PI3K–AKT, IR-A, and β-cell insulin production found no passage linking glucose-handling defects to the β-cell mechanism claimed here. The reported glucose-uptake pathway is a different setting, not a contradiction of the claim. (LLM, conf=0.74)

  cites [238] Song, D. K., Choi, J. H. & Kim, M.-S. Primary cilia as a signaling platform for control of energy metabolism. Diabetes Metab. J. 42, 117–127 (2018). sourceExperimental — accuracy not yet measured

In the paper

“In fibroblasts, ciliary PDGFRα signalling activates the PI3K–AKT and MEK1/2–ERK1/2–RSK pathways to control directional cell migration, which is achieved by targeting the Na+/H+ exchanger 1, NHE1, to the leading edge of the migrating cells, which project their cilium towards the leading edge and parallel to the path of motility 240, 247–249.”

What the sources say

• ?Not checked — no full text of the sourcecites [240] Heldin, C.-H., Lennartsson, J. & Westermark, B. Involvement of platelet-derived growth factor ligands and receptors in tumorigenesis. J. Intern. Med. 283, 16–44 (2018). source
• ?Not checked — no full text of the sourcecites [247] Nielsen, B. S. et al. PDGFRβ and oncogenic mutant PDGFRα D842V promote disassembly of primary cilia through a PLCγ- and AURKA-dependent mechanism. J. Cell Sci. 128, 3543–3549 (2015). source
• Partly supported

  The Results (‘PDGF-AA signals through Akt at the ciliary base’) show PDGF-AA-dependent PDGFRα and Akt activation, and the Introduction reports that migrating fibroblasts orient their cilia toward the leading edge. The Discussion (‘Conclusions and perspectives’) describes MEK1/2–ERK1/2 signaling and its connection through RSK to NHE1, but treats a link from ciliary signaling to leading-edge NHE1 events as a possibility or hypothesis. It does not establish that ciliary PDGFRα controls migration by targeting NHE1 to the leading edge. No page numbers are provided in our copy. (LLM, conf=0.88)

  cites [248] Schneider, L. et al. Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts. Cell. Physiol. Biochem. 25, 279–292 (2010). sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction and Discussion support ciliary PDGFR-α signaling and a role for NHE1 activity in directional fibroblast migration; the Discussion also reports ERK1/2 and PI3K–Akt activation. But it describes p90RSK as a possible link to NHE1, and says increased NHE1 targeting to the leading-edge membrane after PDGF-AA was not convincingly observed. The claim presents those proposed mechanisms as established. (LLM, conf=0.88)

  cites [249] Schneider, L. et al. The Na+/H+ exchanger NHE1 is required for directional migration stimulated via PDGFR-α in the primary cilium. J. Cell Biol. 185, 163–176 (2009). sourceExperimental — accuracy not yet measured

In the paper

“Consequently, defects in the formation of primary cilia by depletion of IFT-B proteins such as IFT88 and IFT172 block PDGFRα activation 247, 250, rendering the cells unable to respond and move towards a gradient of PDGF-AA 247.”

What the sources say

• ?Not checked — no full text of the sourcecites [247] Nielsen, B. S. et al. PDGFRβ and oncogenic mutant PDGFRα D842V promote disassembly of primary cilia through a PLCγ- and AURKA-dependent mechanism. J. Cell Sci. 128, 3543–3549 (2015). source
• Partly supported

  The Cell cultures section identifies Tg737 as encoding IFT88 and says mutant fibroblasts form no or stunted cilia. The ciliary PDGFRαα signaling section says these cells cannot activate the receptor in response to PDGF-AA and lack chemotaxis toward a PDGF-AA gradient. Our copy does not establish the same result for depletion of IFT172. (LLM, conf=0.88)

  cites [250] Clement, D. L. et al. PDGFRα signaling in the primary cilium regulates NHE1-dependent fibroblast migration via coordinated differential activity of MEK1/2–ERK1/2–p90RSK and AKT signaling pathways. J. Cell Sci. 126, 953–965 (2013). sourceExperimental — accuracy not yet measured

In the paper

“NPHP4 was reported to stabilize the E3 PHD finger domain E3 ubiquitin ligase JADE1 and promote its nuclear translocation 213.”

What the sources say

• ?Could not verify

  The Results section on DVL proteins discusses NPHP4 in relation to DVL2 and DVL3 degradation, not JADE1. Searches for JADE1 and for the claimed stabilization and nuclear translocation found no passage addressing that relationship in our copy. (LLM, conf=0.76)

  cites [213] Patnaik, S. R. et al. RPGR protein complex regulates proteasome activity and mediates store-operated calcium entry. Oncotarget 9, 23183–23197 (2018). sourceExperimental — accuracy not yet measured

In the paper

“NPHP2 promotes WNT–PCP signalling by facilitating fzd8-mediated recruitment of Dvl to the membrane, and that proximal pronephros extension is disrupted by morpholino-mediated depletion of NPHP2 199, although normal WNT–β-catenin signalling was unaffected in this study.”

What the sources say

• Partly supported

  The indexed text (section labeled Abstract; page unavailable) supports an involvement of inversin/NPHP2 in noncanonical Wnt signaling and reports that morpholino depletion causes pronephric duct cysts. It does not report fzd8-mediated recruitment of Dvl or disrupted proximal pronephros extension. Contrary to the claim that canonical Wnt–β-catenin signaling was unaffected, it reports increased β-catenin–TCF target-gene expression after inversin depletion. (LLM, conf=0.87)

  cites [199] Simons, M. et al. Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat. Genet. 37, 537–543 (2005). sourceExperimental — accuracy not yet measured

In the paper

“RAB11 285, which is responsible for endosomal recycling of TGFβ receptors 286, is recruited to the cilium in a process that is mediated by the subdistal appendage protein, CEP128 287. Consequently, loss of CEP128 leads to impaired phosphorylation of R-SMADs, which in zebrafish is associated with defective organ development 287.”

What the sources say

• Partly supported

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

  cites [285] Mitchell, H., Choudhury, A., Pagano, R. E. & Leof, E. B. Ligand-dependent and -independent transforming growth factor-β receptor recycling regulated by clathrin-mediated endocytosis and Rab11. Mol. Biol. Cell 15, 4166–4178 (2004). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [287] Miyazawa, K. & Miyazono, K. Regulation of TGF-β family signaling by inhibitory smads. Cold Spring Harb. Perspect. Biol. 9, a022095 (2017). source

In the paper

“Further, endothelial primary cilia, which function as flow sensors in the vasculature and contribute to blood–brain barrier integrity 276–279, counteract endothelial-to-mesenchymal transition in a process that is associated with reduced canonical TGFβ signalling in the endocardial cushion area 280, whereas endothelial primary cilia cooperate with BMP signalling to stabilize vessel connections in”

What the sources say

• ?Not checked — no full text of the sourcecites [276] Goetz & Jacky, G. et al. Endothelial cilia mediate low flow sensing during zebrafish vascular development. Cell Rep. 6, 799–808 (2014). source
• Partly supported

  Split into 3 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  cites [277] Kallakuri, S. et al. Endothelial cilia are essential for developmental vascular integrity in zebrafish. J. Am. Soc. Nephrol. 26, 864–875 (2015). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [278] Hierck, B. P. et al. Primary cilia sensitize endothelial cells for fluid shear stress. Dev. Dyn. 237, 725–735 (2008). source
• Partly supported

  Split into 3 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  cites [279] Egorova, A. D. et al. Lack of primary cilia primes shear-induced endothelial-to-mesenchymal transition. Circ. Res. 108, 1093–1101 (2011). sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 3 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  cites [280] Vion, A.-C. et al. Primary cilia sensitize endothelial cells to BMP and prevent excessive vascular regression. J. Cell Biol. 217, 1651–1665 (2018). sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [281] Kawasaki, M. et al. TGF-β suppresses Ift88 expression in chondrocytic ATDC5 cells. J. Cell. Physiol. 230, 2788–2795 (2015). source

In the paper

“These results suggest the existence of a biochemical and functional relationship between IFT20 and CBL proteins in ciliary receptor sorting and modulation of PDGFRα signalling, which when defective underlies tumorigenic signalling in various tissues 239.”

What the sources say

• ?Could not verify

  The Conclusion (page not provided) discusses selective signaling through insulin receptor isoforms IR-A and IR-B, not ciliary receptor sorting. Searches for IFT20, CBL, PDGFRα and tumorigenic signaling found no passage in our copy addressing the attributed relationship. (LLM, conf=0.78)

  cites [239] Leibiger, B. et al. Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic beta cells. Mol. Cell 7, 559–570 (2001). sourceExperimental — accuracy not yet measured

In the paper

“The mechanisms that control the balanced output of ciliary signalling described in this Review might also apply to other pathways such as Hippo and Notch signalling pathways or those regulated by receptors of extracellular matrix molecules, which also have been linked to primary cilia in various cell types and tissues 23, 291, 292.”

What the sources say

• Partly supported

  The Introduction links Notch and Hippo signalling to primary cilia, and the TGF-β/BMP signalling section describes ciliary control of balanced signalling output. The paper does not substantiate the additional claim that pathways regulated by receptors of extracellular-matrix molecules are linked to primary cilia in various cell types and tissues. (LLM, conf=0.84)

  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). sourceExperimental — accuracy not yet measured
• Supported

  The citation supports the extracellular-matrix-receptor part of the sentence, not necessarily its Hippo or Notch examples. Section 2 says cilia in some cell types display integrin receptors and NG2, allowing responses to extracellular matrix; the Abstract also describes integrin and cadherin family members on the ciliary membrane. (LLM, conf=0.90)

  cites [291] Seeger-Nukpezah, T. & Golemis, E. A. The extracellular matrix and ciliary signaling. Curr. Opin. Cell Biol. 24, 652–661 (2012). source
• Partly supported

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

  cites [292] Wood, C. R. & Rosenbaum, J. L. Ciliary ectosomes: transmissions from the cell’s antenna. Trends Cell Biol. 25, 276–285 (2015). sourceExperimental — accuracy not yet measured

In the paper

“Finally, the E3 ubiquitin ligase SMURF1 negatively regulates phosphorylation of SMAD1/5/8 at primary cilia to control cell-type specification during in vivo heart development, which in Smurf1−/− mouse embryos is associated with delayed outflow tract septation 273.”

What the sources say

• ?Could not verify

  The Results section on ciliary trafficking addresses CerS4, Smad7, TGF-β receptors, and cancer-cell migration, not SMURF1 regulation of SMAD1/5/8 during heart development. Searches for SMURF1, Smurf1−/− embryos, and outflow tract septation found no passage addressing the claim. The available passages have no page numbers. (LLM, conf=0.76)

  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

“Specific receptors and associated signal transduction proteins can also localize to primary cilia in a cell type-dependent manner; available evidence suggests that the ciliary constellation of these proteins can temporally change to allow the cell to adapt to specific developmental and homeostatic cues.”

In the paper

“The cilium is enclosed by a membrane that is continuous with the plasma membrane but has a unique lipid and receptor composition that enables the cilium to detect changes in the extracellular environment and convey signalling information to the cell to regulate diverse cellular, developmental and physiological processes.”

In the paper

“The axoneme of a primary cilium contains a ring of nine outer microtubule doublets (known as a 9+0 axoneme), whereas the axoneme of a motile cilium has nine outer microtubule doublets around two central microtubule singlets (called a 9+2 axoneme).”

In the paper

“Primary cilia project in a single copy from the surface of most vertebrate cell types; they detect and transmit extracellular cues to regulate diverse cellular processes during development and to maintain tissue homeostasis.”

What the sources say

• ?Not checked — no full text of the sourcecites [1] Satir, P. & Christensen, S. T. Overview of structure and function of mammalian cilia. Annu. Rev. Physiol. 69, 377–400 (2007). source

In the paper

“The primary cilium is a microtubule-based, non-motile organelle that extends as a solitary unit from the basal body (derived from the centrosomal mother centriole of most cell types in the human body 1.”

What the sources say

• ?Not checked — no full text of the sourcecites [1] Satir, P. & Christensen, S. T. Overview of structure and function of mammalian cilia. Annu. Rev. Physiol. 69, 377–400 (2007). source

In the paper

“The basal body is a modified centriole that contains specialized structures at its distal end that regulate critical aspects of ciliary biogenesis and function.”

In the paper

“The IFT system was discovered in 1993 following the observation of a continuous movement of particles, sandwiched between the flagellar membrane and axonemal outer doublet microtubules, from the flagellar base to tip (anterograde IFT) and back (retrograde IFT) in Chlamydomonas reinhardtii flagella32.”

What the sources say

• ?Not checked — no full text of the sourcecites [32] Kozminski, K. G., Johnson, K. A., Forscher, P. & Rosenbaum, J. L. A motility in the eukaryotic flagellum unrelated to flagellar beating. Proc. Natl Acad. Sci. USA 90, 5519–5523 (1993). source

In the paper

“These findings suggest that SHH-mediated activation and removal of PTCH1 from cilia might increase the availability of endogenous SMO ligands — most likely cholesterol or cholesterol derivatives — in the ciliary membrane, thereby leading to activation of SMO in cilia.”

In the paper

“Activation of the SHH pathway by formation of the GLI transcriptional activator (GLIA) and basal repression of the SHH pathway by GLI transcriptional repressor (GLIR) are both dependent on the primary cilium 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

“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

• ?Not checked — no full text of the sourcecites [81] Barr, M. M. & Sternberg, P. W. A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans. Nature 401, 386–389 (1999). source

In the paper

“Although SHH secretion from distinct regions, such as the purkinje neurons in the postnatal cerebellum and the zone of polarizing activity in limb buds, patterns these tissues, each of these tissues expresses low or no SHH at distinct stages of development.”

In the paper

“which might increase sensitivity to fluid flow 161 and inhibit cystogenesis.”

What the sources say

• ?Not checked — no full text of the sourcecites [161] Cramer, M. T. & Guay-Woodford, L. M. Cystic kidney disease: a primer. Adv. Chronic Kidney Dis. 22, 297–305 (2015). source

In the paper

“Thus, active repression of HH pathway by GPR161 regulates tissue architecture, whereas pathway de-repression contributes to disease pathogenesis.”

In the paper

“direct coupling of this subunit to PKA in this compartment might enhance the ability of GPR161 to activate PKA via constitutive cAMP signalling.”

In the paper

“Activation of D5 caused an increase in calcium levels in the cilium along with an actin-mediated increase in cilia length”

What the sources say

• ?Not checked — no full text of the sourcecites [161] Cramer, M. T. & Guay-Woodford, L. M. Cystic kidney disease: a primer. Adv. Chronic Kidney Dis. 22, 297–305 (2015). source

In the paper

“raising the fascinating possibility that ciliary GPCR signals might be transmitted between cells.”

In the paper

“Interneurons lacking ARL13B also show disrupted ciliary calcium dynamics and a dramatic reduction in ciliary localization of SSTR3 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

“Disruption of cilia on trophoblast cells ameliorates EG-VEGF-induced activation of ERK1/2, MMP upregulatoin, and cell invasion 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

“BBS mutant mice that lack NPY2R-positive cilia are obese and do not respond to NPY2R ligand 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

“Treatment of trophoblast cells with EG-VEGF activates ERK1/2 signalling to induce upregulation of matrix metalloproteinases (MMPs) and facilitate cell invasion 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

“mutations in MC4R are the most common cause of monogenic obesity in humans, underlying up to 6% of early-onset or severe cases of adult obesity 179.”

What the sources say

• ?Not checked — no full text of the sourcecites [179] Davenport, J. R. et al. Disruption of intraflagellar transport in adult mice leads to obesity and slow-onset cystic kidney disease. Curr. Biol. 17, 1586–1594 (2007). source

In the paper

“loss of ARL13B in interneurons results in reduced dendritic and axonal complexity, disrupted synaptic connectivity, and functional deficits in synaptic activity 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

“expression of SSTR3 in ARL13B-deficient interneuronal cilia rescues the morphological and synaptic connectivity defects, whereas expression of a non-ciliary form of ARL13B with normal GTPase activity does not rescue the developmental defects in ARL13B-deficient interneurons 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

“although multiple lines of evidence from gene knockout or knockdown studies have suggested roles for cilia in regulating WNT signalling, the literature in this field is controversial.”

In the paper

“JADE1 is a negative regulator of WNT–β-catenin signalling that ubiquitinates cytoplasmic and nuclear β-catenin irrespective of its phosphorylation status, thereby promoting its proteasomal degradation 214.”

What the sources say

• ?Not checked — no full text of the sourcecites [214] Borgal, L. et al. The ciliary protein nephrocystin-4 translocates the canonical Wnt regulator Jade-1 to the nucleus to negatively regulate β-catenin signaling. J. Biol. Chem. 287, 25370–25380 (2012). source

In the paper

“Similarly to NPHP2, NPHP3 and NPHP4 restrain DVL-mediated WNT–β-catenin activation in cell culture, and when depleted, induce WNT–PCP defects in vivo (PMID 18371931 and PMID 21498478).”

What the sources say

• ?Not matched

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

  cites PMID 18371931 and PMID 21498478

In the paper

“Thus, NPHP4, in addition to its negative effect on DVL, also negatively regulates β-catenin levels through JADE1.”

In the paper

“Young Bbs4-knockout mice demonstrate impaired glucose handling before the onset of obesity, and ciliary dysfunction induced by knockdown of BBS4 or oral-facial-digital syndrome 1 protein (OFD-1) attenuates first-phase insulin secretion in pancreatic islet cells independent of glucose metabolism 235.”

What the sources say

• ?Not checked — no full text of the sourcecites [235] Wang, H. et al. Hsp90α forms a stable complex at the cilium neck for the interaction of signalling molecules in IGF-1 receptor signalling. J. Cell Sci. 128, 100–108 (2015). source