How to build a signalling organelle: A molecular pathway for biogenesis of the ciliary membrane

Abstract

The primary cilium is a hair‐like projection present at the surface of nearly every vertebrate cell. How such a complex organelle is assembled remains an open question that has become all the more relevant with the emergence of primary cilium dysfunction as the central pathomechanism in a range of inherited disorders characterized by obesity, brain malformations, retinal degeneration, kidney cysts and skeletal abnormalities.Strikingly, all these symptoms coincide in Bardet‐Biedl Syndrome (BBS). However, despite the identification of twelve BBS genes, the molecular basis of BBS had remained elusive. Last year, the discovery of a stable complex of seven BBS proteins (the BBSome) considerably simplified the apparent molecular complexity of BBS. Most tellingly, the BBSome associates the ciliary membrane and with Rabin8, the guanosyl exchange factor for the small GTPase Rab8 and Rab8‐GTP enters the primary cilium to promote extension of the ciliary membrane.Thus, BBS is likely caused by defects in vesicular transport to the primary cilium. With this realization comes a flurry of questions that will be addressed in my presentation: What is the precise molecular activity of the BBSome and Rab8 in this process? What are the effectors of Rab8 involved in ciliogenesis? Does the ARF‐like GTPase ARL6/BBS3 also function in vesicular transport to the cilium?