A lever hypothesis for Synaptotagmin-1 action in neurotransmitter release.

ABSTRACT: Neurotransmitter release is triggered in microseconds by Ca²⁺-binding to the Synaptotagmin-1 C₂ domains and by SNARE complexes that form four-helix bundles between synaptic vesicles and plasma membranes, but the coupling mechanism between Ca²⁺-sensing and membrane fusion is unknown. Release requires extension of SNARE helices into juxtamembrane linkers that precede transmembrane regions (linker zippering) and binding of the Synaptotagmin-1 C₂B domain to SNARE complexes through a 'primary interface' comprising two regions (I and II). The Synaptotagmin-1 Ca²⁺-binding loops were believed to accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers or helping bridge the membranes, but SNARE complex binding orient

SUBMITTER: Jaczynska K 

PROVIDER: S-EPMC11212951 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature