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Publication : Two distinct secretory vesicle-priming steps in adrenal chromaffin cells.

First Author  Liu Y Year  2010
Journal  J Cell Biol Volume  190
Issue  6 Pages  1067-77
PubMed ID  20855507 Mgi Jnum  J:165257
Mgi Id  MGI:4836763 Doi  10.1083/jcb.201001164
Citation  Liu Y, et al. (2010) Two distinct secretory vesicle-priming steps in adrenal chromaffin cells. J Cell Biol 190(6):1067-77
abstractText  Priming of large dense-core vesicles (LDCVs) is a Ca(2+)-dependent step by which LDCVs enter a release-ready pool, involving the formation of the soluble N-ethyl-maleimide sensitive fusion protein attachment protein (SNAP) receptor complex consisting of syntaxin, SNAP-25, and synaptobrevin. Using mice lacking both isoforms of the calcium-dependent activator protein for secretion (CAPS), we show that LDCV priming in adrenal chromaffin cells entails two distinct steps. CAPS is required for priming of the readily releasable LDCV pool and sustained secretion in the continued presence of high Ca(2+) concentrations. Either CAPS1 or CAPS2 can rescue secretion in cells lacking both CAPS isoforms. Furthermore, the deficit in the readily releasable LDCV pool resulting from CAPS deletion is reversed by a constitutively open form of syntaxin but not by Munc13-1, a priming protein that facilitates the conversion of syntaxin to the open conformation. Our data indicate that CAPS functions downstream of Munc13s but also interacts functionally with Munc13s in the LDCV-priming process.
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