A Sequential Vesicle Pool Model with a Single Release Sensor and a Ca2+-Dependent Priming Catalyst Effectively Explains Ca2+-Dependent Properties of Neurosecretion

• DOI: 10.1371/journal.pcbi.1003362
• Publication Date: 2013-12-05T21:24:37Z
• Authors: Alexander M. Walter; Paulo S. Pinheiro; Matthijs Verhage; Jakob B. Sørensen
• Keywords: Secretory Vesicle; Vesicle fusion

Neurotransmitter release depends on the fusion of secretory vesicles with plasma membrane and their contents. The final step displays higher-order Ca(2+) dependence, but also upstream steps depend Ca(2+). After deletion sensor for fast - synaptotagmin-1 slower Ca(2+)-dependent components persist. These findings have provoked working models involving parallel releasable vesicle pools (Parallel Pool Models, PPM) driven by alternative sensors release, no slow acting a pool has been identified. We here propose Sequential Model (SPM), assuming novel action: catalyst that accelerates both forward reverse priming reactions. While account from Readily-Releasable (RRP) under control synaptotagmin-1, origins differ. In SPM component is attributed to refilling RRP Non-Releasable (NRP), whereas PPM attributes separate slowly-releasable pool. Using numerical integration we compared model predictions data mouse chromaffin cells. Like PPM, explains biphasic Ca(2+)-dependence sizes in addition, accounts rapid recovery after strong stimulation, where fails. predicts simultaneous changes rate amplitude seen when mutating SNARE-complex. Finally, it can loss fast- persistence knockout depleted, leading NRP. conclude elusive 'alternative sensor' might be catalyst, sequential effectively properties secretion without or sensors.