Vesicular transport to the primary cilium: basic principles
The membrane of the primary cilium is continuous with the plasma membrane. Despite this continuity, ciliary and plasma membranes contain distinct complements of lipids and proteins, thus making the cilium a bona fide compartment exposed to the extracellular milieu. Consequently, the cilium has been compared to a "cellular antenna" that capture and transduces developmental signals to the inside of the cell. But how do relevant signaling receptors reach the ciliary membrane instead of the plasma membrane? This question of vesicular targeting to the cilium has recently been illuminated by our discovery of two key ciliogenic factors, the BBSome and Rab8. Consistent with the general paradigm of the small GTPases of the Rab family, Rab8 likely mediates the docking and fusion of transport vesicles with the base of the primary cilium. We will test this model by developing in vivo assays for protein trafficking to the cilium and we are in the process of identifying effectors of Rab8 in this process. Conversely to Rab8, the molecular activity of the BBSome is quite poorly understood. The BBSome is a complex of 7 proteins encoded by genes defective in Bardet-Biedl Syndrome (BBS), an disease of the cilium.