Molecular Transport in the Cilium

One of our long-term goals is to understand the dedicated transport mechanism that operates in cilia, known as intraflagellar transport (IFT). IFT is the highly conserved process by which proteins are actively transported along ciliary doublet microtubules by a train-like polymeric assembly of IFT-A, IFT-B and BBSome complexes. IFT-B is implicated in trafficking soluble proteins and axonemal precursors, whereas the BBSome and IFT-A are thought to transport transmembrane and membrane-associated proteins. We are particularly interested in the interplay between these IFT complexes, microtubules, motor proteins, adaptor complexes and their cargoes, and the role of IFT in establishing and maintaining signaling pathways. Using cryo-EM, we have determined structures of the native BBSome complex purified from bovine retina (eLife, 9:e53322) and the native IFT-A complex from Leishmania tarentolae (Cell, 185: 4986–4998). Structures of the BBSome with and without its GTPase partner, ARL6, revealed the GTPase-dependent activation mechanism of the BBSome, unearthed a structural relationship between the BBSome and clathrin adaptor complexes, and provided a molecular explanation for mutations that cause Bardet Biedl Syndrome. The structure of IFT-A revealed the mechanism by which it polymerizes into anterograde IFT trains.