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 α (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, whereas 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 implicates β1 integrin, FAK, and paxillin in mediating the observed 
pro-adhesive effects of αSNAP. These results reveal novel roles for αSNAP in 
regulating ECM adhesion and motility of epithelial cells.