N-Ethylmaleimide-sensitive Factor Attachment Protein α (αSNAP) Regulates Matrix Adhesion and Integrin Processing in Human Epithelial Cells

Integrin-based adhesion to the extracellular matrix (ECM) plays critical roles in controlling differentiation, survival, and motility of epithelial cells. Cells attach to the ECM via dynamic structures called focal adhesions (FA). FA undergo constant remodeling mediated by vesicle trafficking and fusion. A soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) is an essential mediator of membrane fusion; however, its roles in regulating ECM adhesion and cell motility remain unexplored. In this study, we found that siRNA-mediated knockdown of SNAP induced detachment of intestinal epithelial cells, whereas overexpression of SNAP increased ECM adhesion and inhibited cell invasion. Loss of SNAP impaired Golgi-dependent glycosylation and trafficking of 1 integrin and decreased phosphorylation of focal adhesion kinase (FAK) and paxillin resulting in FA disassembly. These effects of SNAP depletion on ECM adhesion were independent of apoptosis and NSF. In agreement with our previous reports that Golgi fragmentation mediates cellular effects of SNAP knockdown, we found that either pharmacologic or genetic disruption of the Golgi recapitulated all the effects of SNAP depletion on ECM adhesion. Furthermore, our data implicates 1 integrin, FAK, and paxillin in mediating the observed pro-adhesive effects of SNAP. These results reveal novel roles for SNAP in regulating ECM adhesion and motility of epithelial cells.