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Molecular origins of synaptotagmin 1 activities on vesicle docking and fusion pore opening.

ABSTRACT: Synaptotagmin 1 (Syt1), a major Ca(2+) sensor in neuroexocytosis, utilizes SNARE- and membrane-binding to regulate vesicle fusion, a required process for neurotransmitter release at the synapse. However, the mechanism by which Syt1 orchestrates SNARE- and membrane- binding to control individual vesicle fusion steps is still unclear. In this study, we used a number of single vesicle assays that can differentiate intermediates of neuroexocytosis, to focus on Syt1 mutants that might impair Syt1-SNARE/PIP2 interaction, Ca(2+)-binding, or membrane penetration. Our results show that, although putative Syt1-SNARE/PIP2 coupling through the polybasic region of the C2B domain is critical for vesicle docking, its disruption does not affect content release. In contrast, Ca(2+)-binding and membrane-penetration mutants significantly reduce content release. Our results thus delineate multiple functions of Syt1 along the pathway of Ca(2+)-triggered exocytosis in unprecedented detail.

SUBMITTER: Lai Y

PROVIDER: S-EPMC4366854 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Molecular origins of synaptotagmin 1 activities on vesicle docking and fusion pore opening.

Lai Ying Y Lou Xiaochu X Diao Jiajie J Shin Yeon-Kyun YK

Scientific reports 20150320

Synaptotagmin 1 (Syt1), a major Ca(2+) sensor in neuroexocytosis, utilizes SNARE- and membrane-binding to regulate vesicle fusion, a required process for neurotransmitter release at the synapse. However, the mechanism by which Syt1 orchestrates SNARE- and membrane- binding to control individual vesicle fusion steps is still unclear. In this study, we used a number of single vesicle assays that can differentiate intermediates of neuroexocytosis, to focus on Syt1 mutants that might impair Syt1-SNA ...[more]

PMID: 25791821

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