The BBSome controls IFT assembly and turnaround in cilia

Abstract

The bidirectional movement of intraflagellar transport (IFT) particles, which are composed of motors, IFT-A and IFT-B subcomplexes, and cargos, is required for cilia biogenesis and signaling 1, 2. A successful IFT cycle depends on the massive IFT particle to be properly assembled at the ciliary base and turned around 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 C. 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 3, 4, a group of conserved proteins affected in human Bardet-Biedl syndrome (BBS) 5, assembles IFT complexes at the ciliary base, then binds to anterograde IFT particle in a DYF-2- (an ortholog of human WDR19) and BBS-1-dependent manner, and lastly reaches the ciliary tip to regulate proper IFT recycling. Our results unravel the BBSome as the key player regulating IFT assembly and turnaround in cilia.