The BBSome controls IFT assembly and turnaround in cilia

Nat Cell Biol. 2012 Sep;14(9):950-7. doi: 10.1038/ncb2560. Epub 2012 Aug 26.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bardet-Biedl Syndrome / genetics
  • Bardet-Biedl Syndrome / metabolism*
  • Biological Transport
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Line, Transformed
  • Cilia / genetics
  • Cilia / metabolism*
  • Flagella / genetics
  • Flagella / metabolism*
  • HEK293 Cells
  • Humans
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Protein Transport

Substances

  • Caenorhabditis elegans Proteins