Coordination of Rab8 and Rab11 in primary ciliogenesis

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 vesicu...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-04, Vol.107 (14), p.6346-6351
Main Authors: Knödler, Andreas, Feng, Shanshan, Zhang, Jian, Zhang, Xiaoyu, Das, Amlan, Peränen, Johan, Guo, Wei
Format: Article
Language:English
Subjects:
Antibodies
Biological Sciences
Cell Line
Cell membranes
Cells
Cilia
Cilia - metabolism
Endosomes
Endosomes - metabolism
Epithelial cells
Genetic disorders
Guanosine Triphosphate - metabolism
Humans
Membranes
Mutation
Photoreceptors
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Proteins
rab GTP-Binding Proteins - genetics
rab GTP-Binding Proteins - metabolism
Recycling
Ribonucleic acid
RNA
RNA, Small Interfering - genetics
Small interfering RNA
trans-Golgi Network - metabolism
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1002401107