TY - JOUR
T1 - The BBSome controls IFT assembly and turnaround in cilia
AU - Wei, Qing
AU - Zhang, Yuxia
AU - Li, Yujie
AU - Zhang, Qing
AU - Ling, Kun
AU - Hu, Jinghua
N1 - Funding Information:
We thank the Caenorhabditis Genetics Center, the Japanese Bioresource Project, J. Scholey (University of California, Davis, USA), M. Leroux (Simon Fraser University, Canada) and M. Barr (Rutgers University, USA) for strains; and A. Fire (Stanford University, USA) for GFP vectors. J.H. and co-workers were supported by the National Institutes of Health research grant 1R01DK090038 and P30 center grant P30DK90728, a Pilot and Feasibility Award from the Mayo Clinic Center for Cell Signaling in Gastroenterology (P30DK084567) and the PKD Foundation Young Investigator Award 04YI09a. J.H. was also supported by a FULK Career Development Award, a Zell PKD Research Award and the Upjohn PKD Research Fund. K.L. was supported by the National Cancer Institute (NCI; 1R01CA149039-01A1), Susan G. Komen for the Cure (KG100902) and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK90728).
PY - 2012/9
Y1 - 2012/9
N2 - The bidirectional movement of intraflagellar transport (IFT) particles, which are composed of motors, IFT-A and IFT-B subcomplexes, and cargoes, is required for the biogenesis and signalling of cilia. A successful IFT cycle depends on the proper assembly of the massive IFT particle at the ciliary base and its turnaround from anterograde to retrograde transport at the ciliary tip. However, how IFT assembly and turnaround are regulated in vivo remains elusive. From a whole-genome mutagenesis screen in Caenorhabditis elegans, we identified two hypomorphic mutations in dyf-2 and bbs-1 as the only mutants showing normal anterograde IFT transport but defective IFT turnaround at the ciliary tip. Further analyses revealed that the BBSome (refs,), a group of conserved proteins affected in human Bardet-Biedl syndrome (BBS), assembles IFT complexes at the ciliary base, then binds to the anterograde IFT particle in a DYF-2-(an orthologue of human WDR19) and BBS-1-dependent manner, and lastly reaches the ciliary tip to regulate proper IFT recycling. Our results identify the BBSome as the key player regulating IFT assembly and turnaround in cilia.
AB - The bidirectional movement of intraflagellar transport (IFT) particles, which are composed of motors, IFT-A and IFT-B subcomplexes, and cargoes, is required for the biogenesis and signalling of cilia. A successful IFT cycle depends on the proper assembly of the massive IFT particle at the ciliary base and its turnaround from anterograde to retrograde transport at the ciliary tip. However, how IFT assembly and turnaround are regulated in vivo remains elusive. From a whole-genome mutagenesis screen in Caenorhabditis elegans, we identified two hypomorphic mutations in dyf-2 and bbs-1 as the only mutants showing normal anterograde IFT transport but defective IFT turnaround at the ciliary tip. Further analyses revealed that the BBSome (refs,), a group of conserved proteins affected in human Bardet-Biedl syndrome (BBS), assembles IFT complexes at the ciliary base, then binds to the anterograde IFT particle in a DYF-2-(an orthologue of human WDR19) and BBS-1-dependent manner, and lastly reaches the ciliary tip to regulate proper IFT recycling. Our results identify the BBSome as the key player regulating IFT assembly and turnaround in cilia.
UR - http://www.scopus.com/inward/record.url?scp=84865803552&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865803552&partnerID=8YFLogxK
U2 - 10.1038/ncb2560
DO - 10.1038/ncb2560
M3 - Article
C2 - 22922713
AN - SCOPUS:84865803552
SN - 1465-7392
VL - 14
SP - 950
EP - 957
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 9
ER -