Abstract
Integrin‐based cell‐matrix adhesions play critical roles in mediating differentiation, survival and motility of epithelial cells. Vesicular trafficking is a key mechanism that regulates assembly of integrin‐based cell‐matrix adhesions and cell migration. A soluble N‐ethylmaleimide sensitive factor (NSF) attachment protein alpha (αSNAP) is a critical regulator of vesicle fusion machinery, however, its role in cell‐matrix adhesions remains unexplored. In this study, we found that siRNA‐mediated knockdown of αSNAP induced matrix detachment in several types of epithelial cells that was independent of a key αSNAP binding partner‐NSF. αSNAP silencing impaired proper glycosylation of β1‐integrin and its trafficking to the cell surface, decreased phosphorylation of FAK and Src and caused disassembly of focal adhesions. Pharmacological inhibition of FAK and Src, but not β1‐ integrin knock‐down recapitulated the effects of αSNAP depletion on cell‐matrix adhesions. Loss of αSNAP depletion resulted in Golgi fragmentation. Furthermore, pharmacological disruption of ER‐Golgi trafficking, or depletion of ER‐Golgi associated protein GBF1 induced FAK/Src dephosphorylation and triggered cell detachment. These results reveal a novel role for αSNAP in modulating β1‐integrin trafficking and matrix adhesions of epithelial cells. Supported by NIH grants DK083968 and DK084953 to AII.
Published Version
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