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Article
Nature Cell Biology - 8, 317 - 328 (2006)
Published online: 26 March 2006; | doi:10.1038/ncb1380


There is a Corrigendum (June 2006) associated with this Article.

Regulation of caveolar endocytosis by syntaxin 6-dependent delivery of membrane components to the cell surface

Amit Choudhury1, David L. Marks1, Kirsty M. Proctor2, Gwyn W. Gould2 & Richard E. Pagano1

1  Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street, S.W., Rochester, MN 55905, USA.

2  Henry Wellcome Laboratory of Cell Biology, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland.

Correspondence should be addressed to Richard E. Pagano pagano.richard@mayo.edu

Caveolar endocytosis has an important function in the cellular uptake of some bacterial toxins, viruses and circulating proteins. However, the molecular machinery involved in regulating caveolar uptake is poorly defined. Here, we demonstrate that caveolar endocytosis is regulated by syntaxin 6, a target membrane soluble N-ethylmaleimide attachment protein receptor (t-SNARE) involved in membrane fusion events along the secretory pathway. When syntaxin 6 function was inhibited, internalization through caveolae was dramatically reduced, whereas other endocytic mechanisms were unaffected. Syntaxin 6 inhibition also reduced the presence of caveolin-1 and caveolae at the plasma membrane. In addition, syntaxin 6 inhibition decreased the delivery of GM1 ganglioside (GM1) and glycosylphosphatidylinositol (GPI)–GFP (but not vesicular stomatitis virus-glycoprotein G; VSV-G) protein from the Golgi complex to the plasma membrane. Addition of GM1 to syntaxin 6-inhibited cells resulted in the reappearance of caveolin-1 and caveolae at the plasma membrane, and restored caveolar uptake. These results suggest that syntaxin 6 regulates the delivery of microdomain-associated lipids and proteins to the cell surface, which are required for caveolar endocytosis.

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Nature Cell Biology
ISSN: 1465-7392
EISSN: 1476-4679
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