Affiliation:
1. Institute for Physiology, University of Saarland, 66424 Homburg/Saar, Germany
2. Department of Molecular Neurobiology, Max-Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
Abstract
ComplexinII (CpxII) and SynaptotagminI (SytI) have been implicated in regulating the function of SNARE proteins in exocytosis, but their precise mode of action and potential interplay have remained unknown. In this paper, we show that CpxII increases Ca2+-triggered vesicle exocytosis and accelerates its secretory rates, providing two independent, but synergistic, functions to enhance synchronous secretion. Specifically, we demonstrate that the C-terminal domain of CpxII increases the pool of primed vesicles by hindering premature exocytosis at submicromolar Ca2+ concentrations, whereas the N-terminal domain shortens the secretory delay and accelerates the kinetics of Ca2+-triggered exocytosis by increasing the Ca2+ affinity of synchronous secretion. With its C terminus, CpxII attenuates fluctuations of the early fusion pore and slows its expansion but is functionally antagonized by SytI, enabling rapid transmitter discharge from single vesicles. Thus, our results illustrate how key features of CpxII, SytI, and their interplay transform the constitutively active SNARE-mediated fusion mechanism into a highly synchronized, Ca2+-triggered release apparatus.
Publisher
Rockefeller University Press
Cited by
54 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献