{alpha} SNAP regulates matrix adhesion and integrin processing in human epithelial cells [Cell Biology]

December 5th, 2013 by Naydenov, N. G., Feygin, A., Wang, L., Ivanov, A. I.

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 alpha (αSNAP) 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 αSNAP induced detachment of intestinal epithelial cells, while overexpression of αSNAP increased ECM adhesion and inhibited cell invasion. Loss of αSNAP impaired Golgi-dependent glycosylation and trafficking of β1 integrin and decreased phosphorylation of Focal adhesion kinase (FAK) and paxillin resulting in FA disassembly. These effects of αSNAP depletion on ECM adhesion were independent of apoptosis and NSF. In agreement with our previous reports that Golgi fragmentation mediates cellular effects of αSNAP knockdown, we found that either pharmacologic or genetic disruption of the Golgi recapitulated all the effects of αSNAP depletion on ECM adhesion. Furthermore, our data suggests that FAK inhibition, not β1-integrin dysfunction, is responsible for loss of ECM adhesions in αSNAP depleted cells. These results reveal novel roles for αSNAP in regulating ECM adhesion and motility of epithelial cells.