Vesicle-associated membrane protein 2 mediates trafficking of alpha5beta1 integrin to the plasma membrane.
Integrins are major receptors for cell adhesion to the extracellular matrix (ECM). As transmembrane proteins, the levels of integrins at the plasma membrane or the cell surface are ultimately determined by the balance between two vesicle trafficking events: endocytosis of integrins at the plasma membrane and exocytosis of the vesicles that transport integrins. Here, we report that vesicle-associated membrane protein 2 (VAMP2), a SNARE protein that mediates vesicle fusion with the plasma membrane, is involved in the trafficking of alpha5beta1 integrin. VAMP2 was present on vesicles containing endocytosed beta1 integrin. Small interfering RNA (siRNA) silencing of VAMP2 markedly reduced cell surface alpha5beta1 and inhibited cell adhesion and chemotactic migration to fibronectin, the ECM ligand of alpha5beta1, without altering cell surface expression of alpha2beta1 integrin or alpha3beta1 integrin. By contrast, silencing of VAMP8, another SNARE protein, had no effect on cell surface expression of the integrins or cell adhesion to fibronectin. In addition, VAMP2-mediated trafficking is involved in cell adhesion to collagen but not to laminin. Consistent with disruption of integrin functions in cell proliferation and survival, VAMP2 silencing diminished proliferation and triggered apoptosis. Collectively, these data indicate that VAMP2 mediates the trafficking of alpha5beta1 integrin to the plasma membrane and VAMP2-dependent integrin trafficking is critical in cell adhesion, migration and survival.
Hasan
Nazarul
N
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, 319 Abraham Flexner Way, Room 515, Louisville, KY 40202, USA.
Hu
Chuan
C
D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D049109:Cell Proliferation; D002633:Chemotaxis / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D004338:Drug Combinations; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D039482:Integrin alpha5 / Q000378:metabolism; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D021381:Protein Transport; D011509:Proteoglycans / Q000378:metabolism; D050683:R-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D022161:Transport Vesicles / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000502:physiology*
D024042:Collagen Type I; D004338:Drug Combinations; D005353:Fibronectins; D039482:Integrin alpha5; D039081:Integrin alpha5beta1; D019012:Integrin beta1; D007797:Laminin; D011509:Proteoglycans; D050683:R-SNARE Proteins; D034741:RNA, Small Interfering; C494807:VAMP2 protein, human; C112938:VAMP8 protein, human; D050988:Vesicle-Associated Membrane Protein 2; C059485:matrigel; D003094:Collagen