| The small GTPase Cdc42 is necessary for primary ciliogenesis in renal tubular epithelial cells. | |
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MedLine Citation:
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PMID: 21543338 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Primary cilia are found on many epithelial cell types, including renal tubular epithelial cells, where they participate in flow sensing. Disruption of cilia function has been linked to the pathogenesis of polycystic kidney disease (PKD). We previously demonstrated that the exocyst, a highly conserved eight-protein membrane trafficking complex: localizes to primary cilia of renal tubular epithelial cells; is required for ciliogenesis; biochemically and genetically interacts with polycystin-2, the protein product of PKD2; and, when disrupted, results in MAPK pathway activation both in vitro and in vivo. The small GTPase Cdc42 is a candidate for regulation of the exocyst at the primary cilium. Here, we demonstrate that Cdc42 biochemically interacts with Sec10, a crucial component of the exocyst complex, and that Cdc42 co-localizes with Sec10 at the primary cilium. Expression of dominant negative Cdc42, and shRNA-mediated knockdown of both Cdc42 and Tuba, a Cdc42 GEF, inhibit ciliogenesis in Madin-Darby canine kidney (MDCK) cells. Furthermore, exocyst Sec8 and polycystin-2 no longer localize to primary cilia, or the ciliary region, following Cdc42 and Tuba knockdown. We also show that Sec10 directly interacts with Par6, a member of the Par complex, which, itself, directly interacts with Cdc42. Finally, we show that Cdc42 knockdown results in activation of the MAPK pathway, something observed in cells with dysfunctional primary cilia. These data support a model in which Cdc42 localizes the exocyst to the primary cilium, whereupon the exocyst then targets and docks vesicles carrying proteins necessary for ciliogenesis. |
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Authors:
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Xiaofeng Zuo; Ben Fogelgren; Joshua H Lipschutz |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-4 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Pennsylvania, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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