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Vol. 20, Issue 10, 2522-2529, May 15, 2009

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The Exocyst Protein Sec10 Is Necessary for Primary Ciliogenesis and Cystogenesis In Vitro

Xiaofeng Zuo^*,, Wei Guo, and Joshua H. Lipschutz

*Departments of Medicine and Biology, University of Pennsylvania, Philadelphia, PA 19104; and Department of Medicine and Cell and Molecular Biology Graduate Group, University of Pennsylvania, and the Veterans Administration Medical Center, Philadelphia, PA 19104

Submitted July 28, 2008; Revised February 24, 2009; Accepted March 11, 2009
Monitoring Editor: Francis A. Barr

InCytes from MBC

Primary cilia are found on many epithelial cell types, including renal tubular epithelial cells, in which they are felt to participate in flow sensing and have been linked to the pathogenesis of cystic renal disorders such as autosomal dominant polycystic kidney disease. We previously localized the exocyst, an eight-protein complex involved in membrane trafficking, to the primary cilium of Madin-Darby canine kidney cells and showed that it was involved in cystogenesis. Here, using short hairpin RNA (shRNA) to knockdown exocyst expression and stable transfection to induce exocyst overexpression, we show that the exocyst protein Sec10 regulates primary ciliogenesis. Using immunofluorescence, scanning, and transmission electron microscopy, primary cilia containing only basal bodies are seen in the Sec10 knockdown cells, and increased ciliogenesis is seen in Sec10-overexpressing cells. These phenotypes do not seem to be because of gross changes in cell polarity, as apical, basolateral, and tight junction proteins remain properly localized. Sec10 knockdown prevents normal cyst morphogenesis when the cells are grown in a collagen matrix, whereas Sec10 overexpression results in increased cystogenesis. Transfection with human Sec10 resistant to the canine shRNA rescues the phenotype, demonstrating specificity. Finally, Par3 was recently shown to regulate primary cilia biogenesis. Par3 and the exocyst colocalized by immunofluorescence and coimmunoprecipitation, consistent with a role for the exocyst in targeting and docking vesicles carrying proteins necessary for primary ciliogenesis.

Address correspondence to: Joshua H. Lipschutz (jhlipsch{at}mail.med.upenn.edu)

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InCytes from MBC, May 2009

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