Exceptionally tight membrane-binding may explain the key role of the synaptotagmin-7 C₂A domain in asynchronous neurotransmitter release.

ABSTRACT: Synaptotagmins (Syts) act as Ca²⁺ sensors in neurotransmitter release by virtue of Ca²⁺-binding to their two C₂ domains, but their mechanisms of action remain unclear. Puzzlingly, Ca²⁺-binding to the C₂B domain appears to dominate Syt1 function in synchronous release, whereas Ca²⁺-binding to the C₂A domain mediates Syt7 function in asynchronous release. Here we show that crystal structures of the Syt7 C₂A domain and C₂AB region, and analyses of intrinsic Ca²⁺-binding to the Syt7 C2 domains using isothermal titration calorimetry, did not reveal major differences that could explain functional differentiation between Syt7 and Syt1. However, using liposome titrations under Ca²⁺

SUBMITTER: Voleti R 

PROVIDER: S-EPMC5635908 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature