A Core Complex of BBS Proteins Cooperates with the GTPase Rab8 to Promote Ciliary Membrane Biogenesis

Maxence V Nachury; Alexander V Loktev; Qihong Zhang; Christopher J Westlake; Johan Peränen; Andreas Merdes; Diane C Slusarski; Richard H Scheller; J. Fernando Bazan; Val C Sheffield; Peter K Jackson

doi:10.1016/j.cell.2007.03.053

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A Core Complex of BBS Proteins Cooperates with the GTPase Rab8 to Promote Ciliary Membrane Biogenesis

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A Core Complex of BBS Proteins Cooperates with the GTPase Rab8 to Promote Ciliary Membrane Biogenesis

Maxence V Nachury, Alexander V Loktev, Qihong Zhang, Christopher J Westlake, Johan Peränen, Andreas Merdes, Diane C Slusarski, Richard H Scheller, J. Fernando Bazan, Val C Sheffield, …

Cell (Cambridge), Vol.129(6), pp.1201-1213

06/15/2007

DOI: 10.1016/j.cell.2007.03.053

PMID: 17574030

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Abstract

Primary cilium dysfunction underlies the pathogenesis of Bardet-Biedl syndrome (BBS), a genetic disorder whose symptoms include obesity, retinal degeneration, and nephropathy. However, despite the identification of 12 BBS genes, the molecular basis of BBS remains elusive. Here we identify a complex composed of seven highly conserved BBS proteins. This complex, the BBSome, localizes to nonmembranous centriolar satellites in the cytoplasm but also to the membrane of the cilium. Interestingly, the BBSome is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Strikingly, Rab8GTP enters the primary cilium and promotes extension of the ciliary membrane. Conversely, preventing Rab8GTP production blocks ciliation in cells and yields characteristic BBS phenotypes in zebrafish. Our data reveal that BBS may be caused by defects in vesicular transport to the cilium.

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Title: Subtitle: A Core Complex of BBS Proteins Cooperates with the GTPase Rab8 to Promote Ciliary Membrane Biogenesis
Creators: Maxence V Nachury - Genentech, Inc., South San Francisco, CA 94080, USA
Alexander V Loktev - Genentech, Inc., South San Francisco, CA 94080, USA
Qihong Zhang - Department of Pediatrics and Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA
Christopher J Westlake - Genentech, Inc., South San Francisco, CA 94080, USA
Johan Peränen - Institute of Biotechnology, FIN-00014 University of Helsinki, Finland
Andreas Merdes - Institut de Sciences et Technologies du Médicament de Toulouse, CNRS/Pierre Fabre, 31400 Toulouse, France
Diane C Slusarski - Department of Biological Sciences, University of Iowa, Iowa City, IA 52242, USA
Richard H Scheller - Genentech, Inc., South San Francisco, CA 94080, USA
J. Fernando Bazan - Genentech, Inc., South San Francisco, CA 94080, USA
Val C Sheffield - Department of Pediatrics and Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA
Peter K Jackson - Genentech, Inc., South San Francisco, CA 94080, USA
Resource Type: Journal article
Publication Details: Cell (Cambridge), Vol.129(6), pp.1201-1213
DOI: 10.1016/j.cell.2007.03.053
PMID: 17574030
NLM abbreviation: Cell
ISSN: 0092-8674
eISSN: 1097-4172
Publisher: Elsevier Inc
Language: English
Date published: 06/15/2007
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Biology; Ophthalmology and Visual Sciences
Record Identifier: 9983992064102771

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