CALL FOR PAPERS Protein and Vesicle Trafficking, Cytoskeleton Cleavage of SNAP-25 and VAMP-2 impairs store-operated Ca entry in mouse pancreatic acinar cells
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چکیده
Rosado, Juan A., Pedro C. Redondo, Ginés M. Salido, Stewart O. Sage, and Jose A. Pariente. Cleavage of SNAP-25 and VAMP-2 impairs store-operated Ca entry in mouse pancreatic acinar cells. Am J Physiol Cell Physiol 288: C214–C221, 2005. First published September 8; doi:10.1152/ajpcell.00241.2004.—We recently reported that store-operated Ca entry (SOCE) in nonexcitable cells is likely to be mediated by a reversible interaction between Ca channels in the plasma membrane and the endoplasmic reticulum, a mechanism known as “secretion-like coupling.” As for secretion, in this model the actin cytoskeleton plays a key regulatory role. In the present study we have explored the involvement of the secretory proteins synaptosomeassociated protein (SNAP-25) and vesicle-associated membrane protein (VAMP) in SOCE in pancreatic acinar cells. Cleavage of SNAP-25 and VAMPs by treatment with botulinum toxin A (BoNT A) and tetanus toxin (TeTx), respectively, effectively inhibited amylase secretion stimulated by the physiological agonist CCK-8. BoNT A significantly reduced Ca entry induced by store depletion using thapsigargin or CCK-8. In addition, treatment with BoNT A once SOCE had been activated reduced Ca influx, indicating that SNAP-25 is needed for both the activation and maintenance of SOCE in pancreatic acinar cells. VAMP-2 and VAMP-3 are expressed in mouse pancreatic acinar cells. Both proteins associate with the cytoskeleton upon Ca store depletion, although only VAMP-2 seems to be sensitive to TeTx. Treatment of pancreatic acinar cells with TeTx reduced the activation of SOCE without affecting its maintenance. These findings support a role for SNAP-25 and VAMP-2 in the activation of SOCE in pancreatic acinar cells and show parallels between this process and secretion in a specialized secretory cell type.
منابع مشابه
Cleavage of SNAP-25 and VAMP-2 impairs store-operated Ca2+ entry in mouse pancreatic acinar cells.
We recently reported that store-operated Ca(2+) entry (SOCE) in nonexcitable cells is likely to be mediated by a reversible interaction between Ca(2+) channels in the plasma membrane and the endoplasmic reticulum, a mechanism known as "secretion-like coupling." As for secretion, in this model the actin cytoskeleton plays a key regulatory role. In the present study we have explored the involveme...
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