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Regulation of endothelial cell migration by syntaxin 6‐mediated post‐Golgi transport and delivery of vascular endothelial growth factor receptor‐2 to the plasma membrane
Author(s) -
Choudhury Amit,
Bhattacharya Resham,
Pagano Richard E.,
Mukhopadhyay Debabrata
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb76
Subject(s) - microbiology and biotechnology , syntaxin , golgi apparatus , syntaxin 3 , chemistry , angiogenesis , biology , exocytosis , secretion , biochemistry , endoplasmic reticulum , cancer research
Vascular endothelial growth factor receptor‐2 (VEGFR‐2) plays a key role in vasculogenesis and pathophysiological angiogenesis. The mechanism of secretory transport and delivery of VEGFR‐2 to the plasma membrane is poorly understood. In the present study, using human umbilical vein endothelial cells (HUVECs) we demonstrate that post‐Golgi trafficking of VEGFR‐2 is regulated by syntaxin 6, a t‐SNARE involved in membrane fusion events along the secretory pathway. Inhibition of syntaxin 6 function using recombinant adenoviruses expressing cytosolic inhibitory forms significantly reduces cell surface VEGFR‐2 (but not transferrin receptor) and blocks post‐Golgi transport of HA‐tagged VEGFR‐2 (but not VSV‐G). Inhibitory forms of syntaxins 8, or 12 had no effect on cell surface levels or post‐Golgi trafficking of HA‐tagged VEGFR‐2. VEGFR‐2 and syntaxin 6 co‐localize at Golgi apparatus and co‐immunoprecipitate. HUVECs expressing inhibitory forms of syntaxin 6 completely blocked VEGF‐induced HUVECs proliferation and migration. Together our data support a model in which syntaxin 6 regulate delivery of VEGFR‐2 from the Golgi apparatus to the cell surface thereby regulating VEGF‐induced cell migration and proliferation.