A conserved mechanism for the retrieval of polyubiquitinated proteins from cilia
Open accessPublished version of a preprint
Abstract
The temporospatial distribution of proteins within cilia is regulated by intraflagellar transport (IFT), wherein molecular trains shuttle between the cell body and cilium. Defects in this process impair various signal-transduction pathways and cause ciliopathies. Although K63-linked ubiquitination appears to trigger protein export from cilia, the mechanisms coupling polyubiquitinated proteins to IFT remain unclear. Using a multidisciplinary approach, we demonstrate that a complex of CFAP36, a conserved ciliary protein of previously unknown function, and ARL3, a GTPase involved in ciliary import, binds polyubiquitinated proteins and links them to retrograde IFT trains. CFAP36 uses a coincidence detection mechanism to simultaneously bind two IFT subunits accessible only in retrograde trains. Depleting CFAP36 accumulates K63-linked ubiquitin in cilia and disrupts hedgehog signaling, a pathway reliant on the retrieval of ubiquitinated receptors. These findings advance our understanding of ubiquitin-mediated protein transport and ciliary homeostasis and demonstrate how structural changes in IFT trains achieve cargo selectivity.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890 · see citing works
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Tissue-based map of the human proteome
Uhlén, M., Fagerberg, L., Hallström, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., Sivertsson, Å., Kampf, C., Sjöstedt, E., Asplund, A., et al. (2015) · Science · doi:10.1126/science.1260419 · Cited by 15,286 · see citing works
WebLogo: A Sequence Logo Generator: Figure 1Preprint
Crooks, G. E., Hon, G. C., Chandonia, J., & Brenner, S. E. (2004) · Genome Research · doi:10.1101/gr.849004 · Cited by 12,433 · see citing works
Szklarczyk, D., Kirsch, R., Koutrouli, M., Nastou, K., Mehryary, F., Hachilif, R., Gable, A. L., Fang, T., Doncheva, N. T., Pyysalo, S., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkac1000 · Cited by 9,726 · see citing works
ColabFold - Making protein folding accessible to all
Mirdita, M., Schütze, K., Moriwaki, Y., Heo, L., Ovchinnikov, S., & Steinegger, M. (2021) · doi:10.1101/2021.08.15.456425 · Cited by 9,391 · see citing works
UniProt: the Universal Protein Knowledgebase in 2023
The UniProt Consortium, Bateman, A., Martin, M.-J., Orchard, S., Magrane, M., Ahmad, S., Alpi, E., Bowler-Barnett, E. H., Britto, R., Bye-A-Jee, H., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkac1052 · Cited by 7,210 · see citing works
Deciphering key features in protein structures with the new ENDscript server
Robert, X., & Gouet, P. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku316 · Cited by 7,053 · see citing works
UCSF ChimeraX : Tools for structure building and analysis
Meng, E. C., Goddard, T. D., Pettersen, E. F., Couch, G. S., Pearson, Z., Morris, J. H., & Ferrin, T. E. (2023) · Protein Science · doi:10.1002/pro.4792 · Cited by 4,575 · see citing works
Letunić, I., & Peer Bork, B. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae268 · Cited by 4,529 · see citing works
Protein complex prediction with AlphaFold-Multimer
Evans, R., O’Neill, M., Pritzel, A., Antropova, N., Senior, A., Green, T., Žídek, A., Bates, R., Blackwell, S., Yim, J., et al. (2021) · doi:10.1101/2021.10.04.463034 · Cited by 3,808 · see citing works
A Completely Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at its Core
Zimmermann, L., Stephens, A., Nam, S.-Z., Rau, D., Kübler, J., Lozajic, M., Gabler, F., Söding, J., Lupas, A. N., & Alva, V. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.12.007 · Cited by 2,522 · see citing works
The PRIDE database at 20 years: 2025 update
Pérez‐Riverol, Y., Bandla, C., Kundu, D. J., Kamatchinathan, S., Bai, J., Hewapathirana, S., John, N. S., Prakash, A., Walzer, M., Wang, S., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae1011 · Cited by 2,075 · see citing works
Varadi, M., Bertoni, D., Magana, P., Paramval, U., Pidruchna, I., Radhakrishnan, M., Tsenkov, M., Nair, S., Mirdita, M., Yeo, J., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkad1011 · Cited by 2,052 · see citing works
UniProt: the universal protein knowledgebase
The UniProt Consortium (2018) · Nucleic Acids Research · doi:10.1093/nar/gky092 · Cited by 2,043 · see citing works
CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing
Labun, K., Montague, T. G., Krause, M., Cleuren, Y. N. T., Tjeldnes, H., & Valen, E. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz365 · Cited by 2,009 · see citing works
Advanced methods of microscope control using μManager software
Edelstein, A., Tsuchida, M. A., Amodaj, N., Pinkard, H., Vale, R. D., & Stuurman, N. (2014) · Journal of Biological Methods · doi:10.14440/jbm.2014.36 · Cited by 1,927 · see citing works
Systematic and Quantitative Assessment of the Ubiquitin-Modified Proteome
Kim, W., Bennett, E. J., Huttlin, E. L., Guo, A., Li, J., Possemato, A. P., Sowa, M. E., Rad, R., Rush, A. J., Comb, M. J., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.08.025 · Cited by 1,582 · see citing works
New and continuing developments at PROSITE
Sigrist, C., de Castro, E., Cerutti, L., Cuche, B. A., Hulo, N., Bridge, A., Bougueleret, L., & Xenarios, I. (2012) · Nucleic Acids Res. · doi:10.1093/nar/gks1067 · Cited by 1,562 · see citing works
Comet: An open‐source <scp>MS</scp> / <scp>MS</scp> sequence database search tool
Eng, J. K., Jahan, T. A., & Hoopmann, M. R. (2013) · PROTEOMICS · doi:10.1002/pmic.201200439 · Cited by 1,474 · see citing works
Patched1 Regulates Hedgehog Signaling at the Primary Cilium
Rohatgi, R., Milenkovic, L., & Scott, M. P. (2007) · Science · doi:10.1126/science.1139740 · Cited by 1,426 · see citing works
Finding a "Kneedle" in a Haystack: Detecting Knee Points in System Behavior
Satopää, V., Albrecht, J. R., Irwin, D., & Raghavan, B. (2011) · IEEE International Conference on Distributed Computing Systems Workshops (ICDCSW) · doi:10.1109/icdcsw.2011.20 · Cited by 1,364 · see citing works
Proteomic analysis of a eukaryotic cilium
Pazour, G. J., Agrin, N. S., Leszyk, J., & Witman, G. B. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200504008 · Cited by 1,028 · see citing works
TriTrypDB: a functional genomic resource for the Trypanosomatidae
Aslett, M. A., Aurrecoechea, C., Berriman, M., Brestelli, J. E., Brunk, B. P., Carrington, M., Depledge, D. P., Fischer, S., Gajria, B., Gao, X., et al. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp851 · Cited by 988 · see citing works
Wagner, S., Beli, P., Weinert, B. T., Nielsen, M. L., Cox, J., Mann, M., & Choudhary, C. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.013284 · Cited by 889 · see citing works
Patched acts catalytically to suppress the activity of Smoothened
Taipale, J., Cooper, M. K., Maiti, T., & Beachy, P. A. (2002) · Nature · doi:10.1038/nature00989 · Cited by 794 · see citing works
The cytoplasmic dynein transport machinery and its many cargoes
Reck‐Peterson, S. L., Redwine, W. B., Vale, R. D., & Carter, A. P. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0004-3 · Cited by 660 · see citing works
OMERO: flexible, model-driven data management for experimental biology
Allan, C., Burel, J.-M., Moore, J., Blackburn, C., Linkert, M., Loynton, S., MacDonald, D., Moore, W. J., Neves, C., Patterson, A., et al. (2012) · Nature Methods · doi:10.1038/nmeth.1896 · Cited by 653 · see citing works
MMseqs2 desktop and local web server app for fast, interactive sequence searches
Mirdita, M., Steinegger, M., & Söding, J. (2019) · Bioinformatics · doi:10.1093/bioinformatics/bty1057 · Cited by 618 · see citing works
Jin, H., White, S. R., Shida, T., Schulz, S., Aguiar, M., Gygi, S. P., Bazán, J. F., & Nachury, M. V. (2010) · Cell · doi:10.1016/j.cell.2010.05.015 · Cited by 594 · see citing works
Huang, F., Kirkpatrick, D. S., Jiang, X., Gygi, S. P., & Sorkin, A. D. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.02.018 · Cited by 553 · see citing works
Mukhopadhyay, S., Wen, X., Ratti, N., Loktev, A., Rangell, L., Scales, S. J., & Jackson, P. K. (2013) · Cell · doi:10.1016/j.cell.2012.12.026 · Cited by 486 · see citing works
Hofmann, K., & Falquet, L. (2001) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(01)01835-7 · Cited by 449 · see citing works
Motile and non-motile cilia in human pathology: From function to phenotypes
Mitchison, H. M., & Valente, E. M. (2017) · The Journal of Pathology · doi:10.1002/path.4843 · Cited by 448 · see citing works
Mukhopadhyay, S., Wen, X., Chih, B., Nelson, C. D., Lane, W. S., Scales, S. J., & Jackson, P. K. (2010) · Genes & Development · doi:10.1101/gad.1966210 · Cited by 435 · see citing works
Proteomics of Primary Cilia by Proximity Labeling
Mick, D. U., Rodrigues, R. B., Leib, R. D., Adams, C. M., Chien, A. S., Gygi, S. P., & Nachury, M. V. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.10.015 · Cited by 409 · see citing works
Lechtreck, K.-F., Johnson, E. C., Sakai, T., Cochran, D., Ballif, B. A., Rush, J., Pazour, G. J., Ikebe, M., & Witman, G. B. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200909183 · Cited by 347 · see citing works
Characterization of Two Polyubiquitin Binding Sites in the 26 S Protease Subunit 5a
Young, P., Deveraux, Q. L., Beal, R. E., Pickart, C. M., & Rechsteiner, M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5461 · Cited by 307 · see citing works
Metabolism of the polyubiquitin degradation signal: structure, mechanism, and role of isopeptidase T
Wilkinson, K. D., Tashayev, V. L., O'Connor, L. B., Larsen, C. N., Kasperek, E. M., & Pickart, C. M. (1995) · Biochemistry · doi:10.1021/bi00044a032 · Cited by 297 · see citing works
Tubiana, J., Schneidman-Duhovny, D., & Wolfson, H. J. (2022) · Nature Methods · doi:10.1038/s41592-022-01490-7 · Cited by 274 · see citing works
IFT27 Links the BBSome to IFT for Maintenance of the Ciliary Signaling Compartment
Eguether, T., San Agustin, J. T., Keady, B. T., Jonassen, J. A., Liang, Y., Francis, R., Tobita, K., Johnson, C. A., Abdelhamed, Z. A., Lo, C. W., et al. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.09.011 · Cited by 260 · see citing works
Why do cellular proteins linked to K63‐polyubiquitin chains not associate with proteasomes?
Nathan, J. A., Kim, H. T., Ting, L., Gygi, S. P., & Goldberg, A. L. (2013) · The EMBO Journal · doi:10.1038/emboj.2012.354 · Cited by 253 · see citing works
Insights into ubiquitin chain architecture using Ub-clipping
Swatek, K. N., Usher, J. L., Kueck, A. F., Gladkova, C., Mevissen, T. E. T., Pruneda, J. N., Skern, T., & Komander, D. (2019) · Nature · doi:10.1038/s41586-019-1482-y · Cited by 236 · see citing works
An ARL3–UNC119–RP2 GTPase cycle targets myristoylated NPHP3 to the primary ciliumPreprint
Wright, K. J., Baye, L. M., Olivier-Mason, A., Mukhopadhyay, S., Sang, L., Kwong, M., Wang, W., Pretorius, P. R., Sheffield, V. C., Sengupta, P., et al. (2011) · Genes & Development · doi:10.1101/gad.173443.111 · Cited by 229 · see citing works
Domire, J. S., Green, J. A., Lee, K. G., Johnson, A. D., Askwith, C. C., & Mykytyn, K. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0603-4 · Cited by 217 · see citing works
IFT25 Links the Signal-Dependent Movement of Hedgehog Components to Intraflagellar Transport
Keady, B. T., Samtani, R., Tobita, K., Tsuchya, M., San Agustin, J. T., Follit, J. A., Jonassen, J. A., Subramanian, R., Lo, C. W., & Pazour, G. J. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.04.009 · Cited by 216 · see citing works
A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and Smoothened
Seo, S., Zhang, Q., Bugge, K., Breslow, D. K., Searby, C. C., Nachury, M. V., & Sheffield, V. C. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002358 · Cited by 205 · see citing works
Electron-tomographic analysis of intraflagellar transport particle trains in situ
Pigino, G., Geimer, S., Lanzavecchia, S., Paccagnini, E., Cantele, F., Diener, D. R., Rosenbaum, J. L., & Lupetti, P. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200905103 · Cited by 204 · see citing works
Sato, Y., Yoshikawa, A., Mimura, H., Yamashita, M., Yamagata, A., & Fukai, S. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.160 · Cited by 202 · see citing works
The retinitis pigmentosa 2 gene product is a GTPase-activating protein for Arf-like 3
Veltel, S., Gasper, R., Eisenacher, E., & Wittinghofer, A. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1396 · Cited by 173 · see citing works
De novo identification of mammalian ciliary motility proteins using cryo-EM
Gui, M., Farley, H. J., Anujan, P., Anderson, J. R., Maxwell, D. W., Whitchurch, J. B., Botsch, J. J., Qiu, T., Meleppattu, S., Singh, S., et al. (2021) · Cell · doi:10.1016/j.cell.2021.10.007 · Cited by 156 · see citing works
Self-citationAn atlas of protein homo-oligomerization across domains of life
Schweke, H., Pacesa, M., Levin, T., Goverde, C. A., Kumar, P., Duhoo, Y., Dornfeld, L. J., Dubreuil, B., Georgeon, S., Ovchinnikov, S., et al. (2024) · Cell · doi:10.1016/j.cell.2024.01.022 · Cited by 144 · see citing works
Lechtreck, K. F., Brown, J. M., Sampaio, J. L., Craft, J. M., Shevchenko, A., Evans, J. E., & Witman, G. B. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201207139 · Cited by 140 · see citing works
Zhang, Q., Nishimura, D. Y., Seo, S., Vogel, T., Morgan, D. A., Searby, C. C., Bugge, K., Stone, E. M., Rahmouni, K., & Sheffield, V. C. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113220108 · Cited by 135 · see citing works
Evans, R. J., Schwarz, N., Nagel‐Wolfrum, K., Uwe Wolfrum, B., Hardcastle, A. J., & Cheetham, M. E. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq012 · Cited by 133 · see citing works
The epidermal growth factor receptor is covalently linked to ubiquitin.
Galcheva-Gargova, Z., Theroux, S. J., & Davis, R. J. (1995) · PubMed · Cited by 132 · see citing works
Zhang, Q., Nishimura, D. Y., Vogel, T., Shao, J., Swiderski, R. E., Yin, T. C., Searby, C. C., Carter, C. S., Kim, G., Bugge, K., et al. (2013) · Journal of Cell Science · doi:10.1242/jcs.111740 · Cited by 126 · see citing works
Christensen, S. T., Morthorst, S. K., Mogensen, J. B., & Pedersen, L. B. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028167 · Cited by 125 · see citing works
The ubiquitin conjugation system is involved in the disassembly of cilia and flagella
Huang, K., Diener, D. R., & Rosenbaum, J. L. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200903066 · Cited by 124 · see citing works
Predictomes, a classifier-curated database of AlphaFold-modeled protein-protein interactions
Schmid, E. W., & Walter, J. C. (2025) · Molecular Cell · doi:10.1016/j.molcel.2025.01.034 · Cited by 120 · see citing works
Craig, R. J., Gallaher, S. D., Shu, S., Salomé, P. A., Jenkins, J. W., Blaby, C., Purvine, S. O., O’Donnell, S., Barry, K., Grimwood, J., et al. (2022) · The Plant Cell · doi:10.1093/plcell/koac347 · Cited by 110 · see citing works
The molecular structure of IFT-A and IFT-B in anterograde intraflagellar transport trains
Lacey, S. E., Foster, H. E., & Pigino, G. (2023) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00905-5 · Cited by 110 · see citing works
Wingfield, J. L., Mengoni, I., Bomberger, H. E., Jiang, Y., Walsh, J. D., Brown, J., Picariello, T., Cochran, D. A., Zhu, B., Pan, J., et al. (2017) · eLife · doi:10.7554/elife.26609 · Cited by 106 · see citing works
GAT (GGA and Tom1) Domain Responsible for Ubiquitin Binding and Ubiquitination
Shiba, Y., Katoh, Y., Shiba, T., Yoshino, K., Takatsu, H., Kobayashi, H., Shin, H., Soichi Wakatsuki, A., & Nakayama, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311702200 · Cited by 104 · see citing works
A monomeric StayGold fluorescent protein
Ivorra-Molla, E., Akhuli, D., McAndrew, M. B. L., Scott, W., Kumar, L., Palani, S., Mishima, M., Crow, A., & Balasubramanian, M. K. (2023) · Nature Biotechnology · doi:10.1038/s41587-023-02018-w · Cited by 99 · see citing works
Ubiquitin chains earmark GPCRs for BBSome-mediated removal from cilia
Shinde, S. R., Nager, A. R., & Nachury, M. V. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.202003020 · Cited by 96 · see citing works
Hansen, J. N., Rassmann, S., Stüven, B., Jurisch‐Yaksi, N., & Wachten, D. (2021) · The European Physical Journal E · doi:10.1140/epje/s10189-021-00031-y · Cited by 90 · see citing works
Time-resolved proteomics profiling of the ciliary Hedgehog response
May, E. A., Kalocsay, M., d'Auriac, I. G., Schuster, P. S., Gygi, S. P., Nachury, M. V., & Mick, D. U. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202007207 · Cited by 86 · see citing works
Ubiquitin links smoothened to intraflagellar transport to regulate Hedgehog signaling
Desai, P. B., Stuck, M. W., Lv, B., & Pazour, G. J. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.201912104 · Cited by 81 · see citing works
Interactions of TOM1L1 with the Multivesicular Body Sorting Machinery
Puertollano, R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m412481200 · Cited by 80 · see citing works
ARL3 Mutations Cause Joubert Syndrome by Disrupting Ciliary Protein Composition
Alkanderi, S., Molinari, E., Shaheen, R., ElMaghloob, Y., Stephen, L. A., Sammut, V., Ramsbottom, S. A., Srivastava, S., Cairns, G., Edwards, N., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.08.015 · Cited by 80 · see citing works
Vasquez, S. S. V., van Dam, J., & Wheway, G. (2021) · Molecular Biology of the Cell · doi:10.1091/mbc.e21-05-0226 · Cited by 67 · see citing works
Proteomic snapshot of the EGF‐induced ubiquitin network
Argenzio, E., Bange, T., Oldrini, B., Bianchi, F., Peesari, R., Mari, S., Fiore, P. P. D., Mann, M., & Polo, S. (2011) · Molecular Systems Biology · doi:10.1038/msb.2010.118 · Cited by 59 · see citing works
Isolation of Chlamydomonas Flagella
Craige, B., Brown, J., & Witman, G. B. (2013) · Current Protocols in Cell Biology · doi:10.1002/0471143030.cb0341s59 · Cited by 59 · see citing works
VCP/p97-associated proteins are binders and debranching enzymes of K48–K63-branched ubiquitin chains
Lange, S. M., McFarland, M. R., Lamoliatte, F., Carroll, T. D., Krshnan, L., Pérez‐Ràfols, A., Kwaśna, D., Shen, L., Wallace, I. R., Cole, I. S., et al. (2024) · Nature Structural & Molecular Biology · doi:10.1038/s41594-024-01354-y · Cited by 58 · see citing works
Self-citationPruś, G., Satpathy, S., Weinert, B. T., Narita, T., & Choudhary, C. (2024) · Cell · doi:10.1016/j.cell.2024.03.024 · Cited by 49 · see citing works
Total Internal Reflection Fluorescence (TIRF) Microscopy of Chlamydomonas Flagella
Engel, B. D., Lechtreck, K. F., Sakai, T., Ikebe, M., Witman, G. B., & Marshall, W. F. (2009) · Methods in cell biology · doi:10.1016/s0091-679x(08)93009-0 · Cited by 47 · see citing works
Lauer, J. L., Segeletz, S., Cezanne, A., Guaitoli, G., Raimondi, F., Gentzel, M., Alva, V., Habeck, M., Kalaidzidis, Y. L., Ueffing, M., et al. (2019) · eLife · doi:10.7554/elife.46302 · Cited by 45 · see citing works
Strom, S. P., Clark, M. J., Martinez, A., Garcia, S., Abelazeem, A. A., Matynia, A., Parikh, S., Sullivan, L. S., Bowne, S. J., Daiger, S. P., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0150944 · Cited by 44 · see citing works
E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened
Lv, B., Stuck, M. W., Desai, P. B., Cabrera, O. A., & Pazour, G. J. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202010177 · Cited by 42 · see citing works
Li, B., Rauhauser, A. A., Dai, J., Sakthivel, R., Igarashi, P., Jetten, A. M., & Attanasio, M. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr339 · Cited by 42 · see citing works
Cargo adapters expand the transport range of intraflagellar transport
Lechtreck, K. F. (2022) · Journal of Cell Science · doi:10.1242/jcs.260408 · Cited by 40 · see citing works
Lacey, S. E., Graziadei, A., & Pigino, G. (2024) · Cell · doi:10.1016/j.cell.2024.06.041 · Cited by 40 · see citing works
Transport and barrier mechanisms that regulate ciliary compartmentalization and ciliopathies
Moran, A. L., Louzao-Martinez, L., Norris, D. P., Peters, D. J. M., & Blacque, O. E. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00773-2 · Cited by 39 · see citing works
Cilia as Wnt signaling organelles
Niehrs, C., Silva, F. D., & Seidl, C. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2024.04.001 · Cited by 38 · see citing works
The ancestral ESCRT protein TOM1L2 selects ubiquitinated cargoes for retrieval from cilia
Shinde, S. R., Mick, D. U., Aoki, E., Rodrigues, R. B., Gygi, S. P., & Nachury, M. V. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.03.003 · Cited by 37 · see citing works
Ciliary signaling cascades in photoreceptors
Yildiz, O., & Khanna, H. (2012) · Vision Research · doi:10.1016/j.visres.2012.08.007 · Cited by 31 · see citing works
Obayashi, T., Kodate, S., Hibara, H., Kagaya, Y., & Kinoshita, K. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac983 · Cited by 31 · see citing works
The molecular architecture of the ciliary transition zones
Mercey, O., Mukherjee, S., Guichard, P., & Hamel, V. (2024) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2024.102361 · Cited by 30 · see citing works
CilioGenics: an integrated method and database for predicting novel ciliary genes
Pir, M. S., Begar, E., Yenisert, F., Demirci, H. C., Korkmaz, M., Karaman, A., Tsiropoulou, S., Firat‐Karalar, E. N., Blacque, O. E., Öner, Ş. S., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae554 · Cited by 30 · see citing works
The Interaction of CCDC104/BARTL1 with Arl3 and Implications for Ciliary Function
Lokaj, M., Kösling, S. K., Koerner, C., Lange, S. M., van Beersum, S. E. C., van Reeuwijk, J., Roepman, R., Horn, N., Ueffing, M., Boldt, K., et al. (2015) · Structure · doi:10.1016/j.str.2015.08.016 · Cited by 29 · see citing works
Self-citationEfficient precision editing of endogenous Chlamydomonas reinhardtii genes with CRISPR-Cas
Nievergelt, A. P., Diener, D. R., Bogdanova, A. I., Brown, T., & Pigino, G. (2023) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100562 · Cited by 29 · see citing works
ARL3 mediates BBSome ciliary turnover by promoting its outward movement across the transition zone
Liu, Y., Sun, W.-Y., Xue, B., Zhang, R., Li, W., Xie, X., & Fan, Z. (2022) · The Journal of Cell Biology · doi:10.1083/jcb.202111076 · Cited by 24 · see citing works
DominantARL3-related retinitis pigmentosa
Holtan, J. P., Teigen, K., Aukrust, I., Bragadóttir, R., & Houge, G. (2019) · Ophthalmic Genetics · doi:10.1080/13816810.2019.1586965 · Cited by 21 · see citing works
Naharros, I. O., Das, T., Castro, R. A., Bazán, J. F., Vaisse, C., & Nachury, M. V. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3003025 · Cited by 18 · see citing works
McCafferty, C. L., Papoulas, O., Lee, C., Bui, K. H., Taylor, D. W., Marcotte, E. M., & Wallingford, J. B. (2024) · Developmental Cell · doi:10.1016/j.devcel.2024.11.019 · Cited by 12 · see citing works
ARL3 GTPases facilitate ODA16 unloading from IFT in motile cilia
Huang, Y., Dong, X., Sun, S., Lim, T. K., Lin, Q., & He, C. Y. (2024) · Science Advances · doi:10.1126/sciadv.adq2950 · Cited by 9 · see citing works
A rare TTC30B variant is identified as a candidate for synpolydactyly in a Chinese pedigree
Du, Y., Chen, F., Zhang, J., Lin, Z., Ma, Q., Guisheng, X., Xiao, D., Gui, Y., Yang, J. H., & Wan, S. (2019) · Bone · doi:10.1016/j.bone.2019.07.012 · Cited by 8 · see citing works
Isolation of Leishmania Promastigote Flagella
Beneke, T., Demay, F., Wheeler, R. J., & Gluenz, E. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0294-2_29 · Cited by 7 · see citing works
Molecular basis for the activation of outer dynein arms in cilia
Issa, K. H. B., Ren, M., Burnet, B., Lu, H., Melia, C., Heesom, K., Roberts, A. J., Roy, S., & Mali, G. R. (2025) · Nature Structural & Molecular Biology · doi:10.1038/s41594-025-01680-9 · Cited by 6 · see citing works
Hedgehog target genes regulate lipid metabolism to drive basal cell carcinoma and medulloblastomaPreprint
Daggubati, V., Vykunta, A., Choudhury, A., Qadeer, Z. A., Mirchia, K., Saulnier, O., Zakimi, N., Hines, K. M., Paul, M., Wang, L., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3058335/v1 · Cited by 4 · see citing works
Wang, J., Kidmose, R. T., Boegholm, N., Zacharia, N. K., Thomsen, M. B., Christensen, A., Malik, T., Lechtreck, K. F., & Lorentzen, E. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.108237 · Cited by 3 · see citing works
Flagged first, then by citations
2 of the 105 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Design principles of ciliary signaling
Ott, C. M., & Lippincott‐Schwartz, J. (2025) · Journal of Cell Science · doi:10.1242/jcs.264325 · Cited by 14 · see citing works
Proteome-wide in silico screening for human protein-protein interactionsPreprint
Schmid, E. W., Zhu, H., Ryu, E., Lim, Y., Smogorzewska, A., Brown, A., & Walter, J. C. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.10.687652 · Cited by 12 · see citing works
Self-citationLi, Z., Zhu, X., Liao, W., Jiang, R., Sang, E., Zhu, J., Sun, G., Lu, Z., Wang, C., Jiang, Y., et al. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104106 · Cited by 3 · see citing works
Structure Makes a Difference: IFT Complex in Ciliary Function and Ciliopathy
Liu, Y., Zhang, Y., Ni, H., & Liu, P. (2025) · Cytoskeleton · doi:10.1002/cm.70033 · Cited by 1 · see citing works
Rezi, C. K., Doğanlı, C., Aslanyan, M. G., Chamlali, M., Mary, B., Callesen, N. L., Abu-Khesha, R. R. K., Diwan, G. D., Russell, R. B., Lorentzen, E., et al. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1805468 · Cited by 1 · see citing works
Yenisert, F., & Kaplan, O. I. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.22.671678
Sani, N. A., Cavani, L., Kawu, M., Kabir, M., Rossoni, A., & Peñagaricano, F. (2026) · Journal of Dairy Science · doi:10.3168/jds.2026-28657
Piyush, R., Giri, P., & Shinde, S. R. (2026) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2026.102675
GPCR signaling from a primary cilium perspective
Idevall‐Hagren, O., & Hughes, J. W. (2026) · Pharmacological Reviews · doi:10.1016/j.pharmr.2026.100159
Zhou, H., Terbeck, L., Berical, A. C., Brunet, M., Lange, S. M., Anderson, J., Olbrich, H., Bracht, D. C., Wohlgemuth, K., Rieck, C., et al. (2026) · Science · doi:10.1126/science.aei5957
Self-citationPrimary cilia: master conductors of cellular communication in development and disease
Thomsen, O. K., Pigino, G., Pedersen, L. B., Pazour, G. J., Wachten, D., & Christensen, S. T. (2026) · Nature Reviews Nephrology · doi:10.1038/s41581-026-01129-2
- Authors
- Lange, S. M., Bennett, J. A., Eisert, R. J., & Brown, A.
- Affiliations
- Harvard University (US)
- Corresponding author
- Brown, Alan
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2025-11
- Volume
- 188
- Issue
- 23
- Pages
- 6492-6508.e18
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC12380154
- OpenAlex
- W4413385180
- Cited by
- 11
- References
- 105
- Citations by year
- 2026: 7 · 2025: 4
- FWCI
- 6.47
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 377 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Funders
- Richard and Susan Smith Family Foundation
- Sara Elizabeth O'Brien Trust
- NIH National Institute of General Medical Sciences (R01GM141109, R01GM143183)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- cilia, intraflagellar transport, K63-linked ubiquitination, polyubiquitinated proteins, ARL3, GTPase, coincidence detection, Hedgehog signaling, ciliopathies
- MeSH terms
- Animals, Cilia, Humans, Signal Transduction, ADP-Ribosylation Factors, Protein Transport, Ubiquitin, Mice, Hedgehog Proteins, Ubiquitination
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
