The BBSome controls IFT assembly and turnaround in cilia

• Published in: Nature cell biology Vol. 14; no. 9; pp. 950 - 957
• Main Authors: Wei, Qing, Zhang, Yuxia, Li, Yujie, Zhang, Qing, Ling, Kun, Hu, Jinghua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2012; Nature Publishing Group
• Subjects: 631/208/2489/144; 631/57/2272; 631/80/128/1383; Amino Acid Sequence; Animals; Bardet-Biedl Syndrome - genetics; Bardet-Biedl Syndrome - metabolism; Biological Transport; Biomedical and Life Sciences; Biosynthesis; Caenorhabditis elegans; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cancer Research; Cell Biology; Cell Line, Transformed; Cilia - genetics; Cilia - metabolism; Cilia and ciliary motion; Developmental Biology; Flagella - genetics; Flagella - metabolism; Genomes; HEK293 Cells; Humans; letter; Life Sciences; Mice; Molecular Sequence Data; Mutagenesis; Mutation; Physiological aspects; Protein Transport; Proteins; Recycling; Stem Cells; United States; United States > US; Minnesota
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb2560

Intraflagellar transport (IFT) particles are essential for the biogenesis and maintenance of cilia. They assemble at the cilium base and travel up and down the cilia, turning around at the tip, but the mechanisms that regulate these processes were not clear. Hu and colleagues reveal a role for the BBSome in IFT assembly and turnaround. 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 1 , 2 . 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  3 , 4 ), a group of conserved proteins affected in human Bardet–Biedl syndrome 5 (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.