Silencing of VAMP3 inhibits cell migration and integrin-mediated adhesion.
Integrins are transmembrane receptors for cell adhesion to the extracellular matrix. In cell migration, integrins are endocytosed from the plasma membrane or the cell surface, transported in vesicles and exocytosed actively at the cell front. In the present study, we examined the roles of VAMP3, a SNARE protein that mediates exocytosis, in cell migration and integrin trafficking. Small interfering RNA (siRNA)-induced silencing of VAMP3 inhibited chemotactic cell migration by more than 60% without affecting cell proliferation. VAMP3 silencing reduced the levels of beta1 integrin at the cell surface but had no effect on total cellular beta1 integrin, indicating that VAMP3 is required for trafficking of beta1 integrin to the plasma membrane. Furthermore, VAMP3 silencing diminished cell adhesion to laminin but not to fibronectin or collagen. Taken together, these data suggest that VAMP3-dependent integrin trafficking is crucial in cell migration and cell adhesion to laminin.
Luftman
Kevin
K
Department of Biochemistry & Molecular Biology, University of Louisville School of Medicine, 319 Abraham Flexner Way, Room 515, Louisville, KY 40202, USA.
Hasan
Nazarul
N
Day
Paul
P
Hardee
Deborah
D
Hu
Chuan
C
D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002633:Chemotaxis / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051040:Vesicle-Associated Membrane Protein 3 / Q000235:genetics / Q000502:physiology*
D019012:Integrin beta1; D007797:Laminin; D034741:RNA, Small Interfering; C494946:VAMP3 protein, human; D051040:Vesicle-Associated Membrane Protein 3