A sequential vesicle pool model with a single release sensor and a Ca(2+)-dependent priming catalyst effectively explains Ca(2+)-dependent properties of neurosecretion

PLoS Computational Biology
Alexander M WalterJakob B Sørensen

Abstract

Neurotransmitter release depends on the fusion of secretory vesicles with the plasma membrane and the release of their contents. The final fusion step displays higher-order Ca(2+) dependence, but also upstream steps depend on Ca(2+). After deletion of the Ca(2+) sensor for fast release - synaptotagmin-1 - slower Ca(2+)-dependent release components persist. These findings have provoked working models involving parallel releasable vesicle pools (Parallel Pool Models, PPM) driven by alternative Ca(2+) sensors for release, but no slow release sensor acting on a parallel vesicle pool has been identified. We here propose a Sequential Pool Model (SPM), assuming a novel Ca(2+)-dependent action: a Ca(2+)-dependent catalyst that accelerates both forward and reverse priming reactions. While both models account for fast fusion from the Readily-Releasable Pool (RRP) under control of synaptotagmin-1, the origins of slow release differ. In the SPM the slow release component is attributed to the Ca(2+)-dependent refilling of the RRP from a Non-Releasable upstream Pool (NRP), whereas the PPM attributes slow release to a separate slowly-releasable vesicle pool. Using numerical integration we compared model predictions to data from mouse chromaff...Continue Reading

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Citations

Dec 18, 2014·Biophysical Journal·Robert D Adams, Amy B Harkins
Dec 20, 2014·Nature Reviews. Neuroscience·Ege T Kavalali
Apr 2, 2016·PLoS Computational Biology·Kashif MahfoozJohn F Wesseling
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Oct 13, 2016·Journal of Neurochemistry·Paulo S PinheiroJakob B Sørensen
Jun 19, 2021·PLoS Computational Biology·Manu KaliaChristine R Rose
Oct 7, 2021·ELife·Abdelmoneim EshraStefan Hallermann

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