Doc2b synchronizes secretion from chromaffin cells by stimulating fast and inhibiting sustained release

P.S. Pinheiro, H. de Wit, A.M. Walter, A.J.A. Groffen, M. Verhage, J.B. Sørensen

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Synaptotagmin-1 and -7 constitute the main calcium sensors mediating SNARE-dependent exocytosis in mouse chromaffin cells, but the role of a closely related calcium-binding protein, Doc2b, remains enigmatic. We investigated its role in chromaffin cells using Doc2b knock-out mice and high temporal resolution measurements of exocytosis. We found that the calcium dependence of vesicle priming and release triggering remained unchanged, ruling out an obligatory role for Doc2b in those processes. However, in the absence of Doc2b, release was shifted from the readily releasable pool to the subsequent sustained component. Conversely, upon overexpression of Doc2b, the sustained component was largely inhibited whereas the readily releasable pool was augmented. Electron microscopy revealed an increase in the total number of vesicles upon Doc2b overexpression, ruling out vesicle depletion as the cause for the reduced sustained component. Further experiments showed that, in the absence of Doc2b, the refilling of the readily releasable vesicle pools is faster, but incomplete. Faster refilling leads to an increase in the sustained component as newly primed vesicles fuse while the [Ca
Original languageEnglish
Pages (from-to)16459-16470
JournalThe Journal of Neuroscience
Volume33
Issue number42
DOIs
Publication statusPublished - 2013

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