{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:15:41Z","timestamp":1787318141833,"version":"build-2736575974"},"reference-count":43,"publisher":"The Company of Biologists","issue":"21","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100008893","name":"University of Iowa","doi-asserted-by":"publisher","award":["14520720200"],"award-info":[{"award-number":["14520720200"]}],"id":[{"id":"10.13039\/100008893","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM114429"],"award-info":[{"award-number":["R01GM114429"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31570721"],"award-info":[{"award-number":["31570721"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chinese Ministry for Foreign Experts","award":["GDW20143100069"],"award-info":[{"award-number":["GDW20143100069"]}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["14521100700"],"award-info":[{"award-number":["14521100700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The primary cilium is a microtubule-based organelle that protrudes from the cell surface and plays essential roles in embryonic development. Ciliogenesis begins with the successive fusion of preciliary vesicles to form ciliary vesicles, which then dock onto the distal end of the mother centriole. Rab proteins have been linked to cilia formation in cultured cells, but not yet in vivo. In the present study, we demonstrate that endocytic recycling protein Rab34 localizes to cilia, and that its mutation results in significant decrease of ciliogenesis in both cultured cells and mice. Rab34 is required for the successive fusion of preciliary vesicles to generate ciliary vesicles and for the migration of the mother centriole from perinuclear region to plasma membrane. We also show that Rab34 mutant mice exhibit polydactyly, and cleft-lip and -palate. These phenotypes are consistent with observations that nonciliated Rab34 mutant cells fail to respond to Hedgehog signaling and that processing of full-length Gli3 to its C-terminally truncated form is reduced in Rab34 mutant embryos. Therefore, Rab34 is required for an early step of ciliary vesicle formation and Hh signaling in vivo.<\/jats:p>\n                  <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/jcs.213710","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T10:08:30Z","timestamp":1539079710000},"source":"Crossref","is-referenced-by-count":35,"title":["Rab34 small GTPase is required for Hedgehog signaling and an early step of ciliary vesicle formation in mouse"],"prefix":"10.1242","volume":"131","author":[{"given":"Shouying","family":"Xu","sequence":"first","affiliation":[{"name":"Weill Medical College of Cornell University 1 Department of Genetic Medicine , , 1300 York Avenue, W404, New York, NY 10065 , USA"},{"name":"Institute of Biological Sciences and Biotechnology, Donghua University 2 , Shanghai 201620 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Weill Medical College of Cornell University 1 Department of Genetic Medicine , , 1300 York Avenue, W404, New York, NY 10065 , USA"},{"name":"College of Veterinary Medicine, Jilin University 3 Department of Veterinary Public Health , , Jilin 130000 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Meng","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences and Biotechnology, Donghua University 2 , Shanghai 201620 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2366-4980","authenticated-orcid":false,"given":"Baolin","family":"Wang","sequence":"additional","affiliation":[{"name":"Weill Medical College of Cornell University 1 Department of Genetic Medicine , , 1300 York Avenue, W404, New York, NY 10065 , USA"},{"name":"Weill Medical College of Cornell University 4 Department of Cell and Developmental Biology , , 1300 York Avenue, W404, New York, NY 10065 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2018,11,8]]},"reference":[{"key":"2024061317585937100_JCS213710C1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028175","article-title":"Primary cilia and mammalian hedgehog signaling","volume":"9","author":"Bangs","year":"2017","journal-title":"Cold Spring Harb. Perspect Biol."},{"key":"2024061317585937100_JCS213710C2","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1242\/jcs.058883","article-title":"Differential role of Rab proteins in ciliary trafficking: Rab23 regulates smoothened levels","volume":"123","author":"Boehlke","year":"2010","journal-title":"J. Cell Sci."},{"key":"2024061317585937100_JCS213710C3","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/S0092-8674(00)80853-3","article-title":"A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube","volume":"101","author":"Briscoe","year":"2000","journal-title":"Cell"},{"key":"2024061317585937100_JCS213710C4","doi-asserted-by":"publisher","first-page":"e6529","DOI":"10.1371\/journal.pone.0006529","article-title":"A versatile viral system for expression and depletion of proteins in mammalian cells","volume":"4","author":"Campeau","year":"2009","journal-title":"PLoS ONE"},{"key":"2024061317585937100_JCS213710C5","doi-asserted-by":"publisher","first-page":"14071","DOI":"10.1073\/pnas.182542899","article-title":"Small molecule modulation of Smoothened activity","volume":"99","author":"Chen","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024061317585937100_JCS213710C6","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1101\/gad.1794109","article-title":"Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved","volume":"23","author":"Chen","year":"2009","journal-title":"Genes Dev."},{"key":"2024061317585937100_JCS213710C7","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1038\/nature04117","article-title":"Vertebrate Smoothened functions at the primary cilium","volume":"437","author":"Corbit","year":"2005","journal-title":"Nature"},{"key":"2024061317585937100_JCS213710C8","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/nature19356","article-title":"High-throughput discovery of novel developmental phenotypes","volume":"537","author":"Dickinson","year":"2016","journal-title":"Nature"},{"key":"2024061317585937100_JCS213710C9","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/35084089","article-title":"Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway","volume":"412","author":"Eggenschwiler","year":"2001","journal-title":"Nature"},{"key":"2024061317585937100_JCS213710C10","doi-asserted-by":"publisher","first-page":"3781","DOI":"10.1091\/mbc.e06-02-0133","article-title":"The intraflagellar transport protein IFT20 is associated with the Golgi complex and is required for cilia assembly","volume":"17","author":"Follit","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"2024061317585937100_JCS213710C11","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.ydbio.2014.04.012","article-title":"Rab23 regulates Nodal signaling in vertebrate left-right patterning independently of the Hedgehog pathway","volume":"391","author":"Fuller","year":"2014","journal-title":"Dev. Biol."},{"key":"2024061317585937100_JCS213710C12","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.cell.2009.03.023","article-title":"The vertebrate primary cilium in development, homeostasis, and disease","volume":"137","author":"Gerdes","year":"2009","journal-title":"Cell"},{"key":"2024061317585937100_JCS213710C13","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1101\/gad.10.3.301","article-title":"Conservation of the hedgehog\/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog","volume":"10","author":"Goodrich","year":"1996","journal-title":"Genes Dev."},{"key":"2024061317585937100_JCS213710C14","doi-asserted-by":"publisher","first-page":"e53","DOI":"10.1371\/journal.pgen.0010053","article-title":"Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function","volume":"1","author":"Haycraft","year":"2005","journal-title":"PLoS Genet."},{"key":"2024061317585937100_JCS213710C15","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1016\/j.cell.2010.05.015","article-title":"The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia","volume":"141","author":"Jin","year":"2010","journal-title":"Cell"},{"key":"2024061317585937100_JCS213710C16","doi-asserted-by":"publisher","first-page":"6346","DOI":"10.1073\/pnas.1002401107","article-title":"Coordination of Rab8 and Rab11 in primary ciliogenesis","volume":"107","author":"Knodler","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024061317585937100_JCS213710C17","doi-asserted-by":"publisher","first-page":"2996","DOI":"10.1242\/jcs.163964","article-title":"A role for Rab23 in the trafficking of Kif17 to the primary cilium","volume":"128","author":"Lim","year":"2015","journal-title":"J. Cell Sci."},{"key":"2024061317585937100_JCS213710C18","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/ncb3109","article-title":"Early steps in primary cilium assembly require EHD1\/EHD3-dependent ciliary vesicle formation","volume":"17","author":"Lu","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"2024061317585937100_JCS213710C19","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1038\/ng.3871","article-title":"Mutations in DZIP1L, which encodes a ciliary-transition-zone protein, cause autosomal recessive polycystic kidney disease","volume":"49","author":"Lu","year":"2017","journal-title":"Nat. Genet."},{"key":"2024061317585937100_JCS213710C20","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1006\/dbio.1996.0300","article-title":"Sonic hedgehog differentially regulates expression of GLI and GLI3 during limb development","volume":"180","author":"Marigo","year":"1996","journal-title":"Dev. Biol."},{"key":"2024061317585937100_JCS213710C21","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1016\/j.cell.2007.03.053","article-title":"A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis","volume":"129","author":"Nachury","year":"2007","journal-title":"Cell"},{"key":"2024061317585937100_JCS213710C22","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.ydbio.2008.11.009","article-title":"Phosphorylation of Gli2 by protein kinase A is required for Gli2 processing and degradation and the Sonic Hedgehog-regulated mouse development","volume":"326","author":"Pan","year":"2009","journal-title":"Dev. Biol."},{"key":"2024061317585937100_JCS213710C23","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1083\/jcb.200107108","article-title":"The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance","volume":"157","author":"Pazour","year":"2002","journal-title":"J. Cell Biol."},{"key":"2024061317585937100_JCS213710C24","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.devcel.2017.12.003","article-title":"CRISPR screens uncover genes that regulate target cell sensitivity to the morphogen sonic hedgehog","volume":"44","author":"Pusapati","year":"2018","journal-title":"Dev. Cell"},{"key":"2024061317585937100_JCS213710C25","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/nrm.2017.60","article-title":"Genes and molecular pathways underpinning ciliopathies","volume":"18","author":"Reiter","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2024061317585937100_JCS213710C26","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1126\/science.1139740","article-title":"Patched1 regulates hedgehog signaling at the primary cilium","volume":"317","author":"Rohatgi","year":"2007","journal-title":"Science"},{"key":"2024061317585937100_JCS213710C27","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1038\/ncb3370","article-title":"Cilium assembly and disassembly","volume":"18","author":"S\u00e1nchez","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"2024061317585937100_JCS213710C28","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/nmeth.3047","article-title":"Improved vectors and genome-wide libraries for CRISPR screening","volume":"11","author":"Sanjana","year":"2014","journal-title":"Nat. Methods"},{"key":"2024061317585937100_JCS213710C29","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1242\/jcs.136903","article-title":"Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis","volume":"127","author":"Sato","year":"2014","journal-title":"J. Cell Sci."},{"key":"2024061317585937100_JCS213710C30","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/j.cub.2009.05.016","article-title":"Control of centriole length by CPAP and CP110","volume":"19","author":"Schmidt","year":"2009","journal-title":"Curr. Biol."},{"key":"2024061317585937100_JCS213710C31","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1083\/jcb.15.2.363","article-title":"Centrioles and the formation of rudimentary cilia by fibroblasts and smooth muscle cells","volume":"15","author":"Sorokin","year":"1962","journal-title":"J. Cell Biol."},{"key":"2024061317585937100_JCS213710C32","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/j.cell.2007.06.027","article-title":"Cep97 and CP110 suppress a cilia assembly program","volume":"130","author":"Spektor","year":"2007","journal-title":"Cell"},{"key":"2024061317585937100_JCS213710C33","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1242\/dev.001966","article-title":"Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning","volume":"134","author":"Vokes","year":"2007","journal-title":"Development"},{"key":"2024061317585937100_JCS213710C34","doi-asserted-by":"publisher","first-page":"4317","DOI":"10.1091\/mbc.e02-05-0280","article-title":"Interorganellar regulation of lysosome positioning by the Golgi apparatus through Rab34 interaction with Rab-interacting lysosomal protein","volume":"13","author":"Wang","year":"2002","journal-title":"Mol. Biol. Cell"},{"key":"2024061317585937100_JCS213710C35","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/S0092-8674(00)80678-9","article-title":"Hedgehog-regulated processing of Gli3 produces an anterior\/posterior repressor gradient in the developing vertebrate limb","volume":"100","author":"Wang","year":"2000","journal-title":"Cell"},{"key":"2024061317585937100_JCS213710C36","doi-asserted-by":"publisher","first-page":"29518","DOI":"10.1074\/jbc.M113.492066","article-title":"Centrosomal protein DZIP1 regulates Hedgehog signaling by promoting cytoplasmic retention of transcription factor GLI3 and affecting ciliogenesis","volume":"288","author":"Wang","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2024061317585937100_JCS213710C37","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.ydbio.2017.08.003","article-title":"Three Tctn proteins are functionally conserved in the regulation of neural tube patterning and Gli3 processing but not ciliogenesis and Hedgehog signaling in the mouse","volume":"430","author":"Wang","year":"2017","journal-title":"Dev. Biol."},{"key":"2024061317585937100_JCS213710C38","doi-asserted-by":"publisher","first-page":"dev164236","DOI":"10.1242\/dev.164236","article-title":"Centrosomal protein Dzip1l binds Cby, promotes ciliary bud formation, and acts redundantly with Bromi to regulate ciliogenesis in the mouse","volume":"146","author":"Wang","year":"2018","journal-title":"Development"},{"key":"2024061317585937100_JCS213710C39","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1128\/MCB.01089-09","article-title":"Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation","volume":"30","author":"Wen","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"2024061317585937100_JCS213710C40","doi-asserted-by":"publisher","first-page":"2759","DOI":"10.1073\/pnas.1018823108","article-title":"Primary cilia membrane assembly is initiated by Rab11 and transport protein particle II (TRAPPII) complex-dependent trafficking of Rabin8 to the centrosome","volume":"108","author":"Westlake","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024061317585937100_JCS213710C41","doi-asserted-by":"publisher","first-page":"e107943","DOI":"10.1371\/journal.pone.0107943","article-title":"Talpid3-binding centrosomal protein Cep120 is required for centriole duplication and proliferation of cerebellar granule neuron progenitors","volume":"9","author":"Wu","year":"2014","journal-title":"PLoS ONE"},{"key":"2024061317585937100_JCS213710C42","doi-asserted-by":"publisher","first-page":"2386","DOI":"10.1093\/hmg\/ddx127","article-title":"Loss of dynein-2 intermediate chain Wdr34 results in defects in retrograde ciliary protein trafficking and Hedgehog signaling in the mouse","volume":"26","author":"Wu","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"2024061317585937100_JCS213710C43","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1083\/jcb.200703047","article-title":"Functional dissection of Rab GTPases involved in primary cilium formation","volume":"178","author":"Yoshimura","year":"2007","journal-title":"J. Cell Biol."}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/jcs.213710","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.213710\/3504094\/jcs213710.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.213710\/2058745\/jcs_213710v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.213710\/3504094\/jcs213710.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T14:27:12Z","timestamp":1718288832000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/131\/21\/jcs213710\/77060\/Rab34-small-GTPase-is-required-for-Hedgehog"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,1]]},"references-count":43,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2018,11,1]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.213710","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.734209399.793554627","asserted-by":"object"}]},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2018,11,1]]},"article-number":"jcs213710"}}