Synaptotagmin-1 drives synchronous Ca²⁺-triggered fusion by C₂B-domain-mediated synaptic-vesicle-membrane attachment.

ABSTRACT: The synaptic vesicle (SV) protein synaptotagmin-1 (Syt1) is the Ca²⁺ sensor for fast synchronous release. Biochemical and structural data suggest that Syt1 interacts with phospholipids and SNARE complex, but the manner in which these interactions translate into SV fusion remains poorly understood. Using flash-and-freeze electron microscopy, which triggers action potentials with light and coordinately arrests synaptic structures with rapid freezing, we found that synchronous-release-impairing mutations in the Syt1 C₂B domain (K325, 327; R398, 399) also disrupt SV-active-zone plasma-membrane attachment. Single action potential induction rescued membrane attachment in these mutants within less than 10 ms through activation of the Syt1 Ca²⁺-binding site. The ra

SUBMITTER: Chang S 

PROVIDER: S-EPMC5742540 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature