Different states of synaptotagmin regulate evoked versus spontaneous release

Hua Bai, Renhao Xue, Huan Bao, Leili Zhang, Arun Yethiraj, Qiang Cui and Edwin R. Chapman ()
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Hua Bai: University of Wisconsin
Renhao Xue: University of Wisconsin
Huan Bao: University of Wisconsin
Leili Zhang: University of Wisconsin
Arun Yethiraj: University of Wisconsin
Qiang Cui: University of Wisconsin
Edwin R. Chapman: University of Wisconsin

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: Abstract The tandem C2-domains of synaptotagmin 1 (syt) function as Ca2+-binding modules that trigger exocytosis; in the absence of Ca2+, syt inhibits spontaneous release. Here, we used proline linkers to constrain and alter the relative orientation of these C2-domains. Short poly-proline helices have a period of three, so large changes in the relative disposition of the C2-domains result from changing the length of the poly-proline linker by a single residue. The length of the linker was varied one residue at a time, revealing a periodicity of three for the ability of the linker mutants to interact with anionic phospholipids and drive evoked synaptic transmission; syt efficiently drove exocytosis when its tandem C2-domains pointed in the same direction. Analysis of spontaneous release revealed a reciprocal relationship between the activation and clamping activities of the linker mutants. Hence, different structural states of syt underlie the control of distinct forms of synaptic transmission.

Date: 2016
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DOI: 10.1038/ncomms10971

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