Regulation of caveolar endocytosis by syntaxin 6-dependent delivery of membrane components to the cell surface.
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.
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street, S.W., Rochester, MN 55905, USA.
Amit
A
Choudhury
David L
DL
Marks
Kirsty M
KM
Proctor
Gwyn W
GW
Gould
Richard E
RE
Pagano
D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D004705:Endocytosis; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006056:Golgi Apparatus; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009841:Oligonucleotides / Q000494:pharmacology; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism*
D051242:Caveolin 1; C028391:G protein, vesicular stomatitis virus; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D009841:Oligonucleotides; D050765:Qa-SNARE Proteins; D014759:Viral Envelope Proteins; D005677:G(M1) Ganglioside