Coordination of Rab8 and Rab11 in primary ciliogenesis

A Knödler, S Feng, J Zhang, X Zhang… - Proceedings of the …, 2010 - National Acad Sciences
A Knödler, S Feng, J Zhang, X Zhang, A Das, J Peränen, W Guo
Proceedings of the national academy of Sciences, 2010National Acad Sciences
Primary cilia are microtubule-based membrane projections located at the surface of many
cells. Defects in primary cilia formation have been implicated in a number of genetic
disorders, such as Bardet-Biedl Syndrome and Polycystic Kidney Disease. Recent studies
have demonstrated that polarized vesicular transport involving Rab8 and its guanine
nucleotide-exchange factor Rabin8 is essential for primary ciliogenesis. Here we report that
Rabin8 is a direct downstream effector of Rab11, which functions in membrane trafficking …
Primary cilia are microtubule-based membrane projections located at the surface of many cells. Defects in primary cilia formation have been implicated in a number of genetic disorders, such as Bardet-Biedl Syndrome and Polycystic Kidney Disease. Recent studies have demonstrated that polarized vesicular transport involving Rab8 and its guanine nucleotide-exchange factor Rabin8 is essential for primary ciliogenesis. Here we report that Rabin8 is a direct downstream effector of Rab11, which functions in membrane trafficking from the trans-Golgi network and recycling endosomes. Rab11, in its GTP-bound form, interacts with Rabin8 and kinetically stimulates the guanine nucleotide-exchange activity of Rabin8 toward Rab8. Rab11 is enriched at the base of the primary cilia and inhibition of Rab11 function by a dominant-negative mutant or RNA interference blocks primary ciliogenesis. Our results suggest that Rab GTPases coordinate with each other in the regulation of vesicular trafficking during primary ciliogenesis.
National Acad Sciences