Different states of synaptotagmin regulate evoked versus spontaneous release

Different states of synaptotagmin regulate evoked versus spontaneous release

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 peri...

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Main Authors: Bai, Hua, Xue, Renhao, Bao, Huan, Zhang, Leili, Yethiraj, Arun, Cui, Qiang, Chapman, Edwin R.
Format: Online
Language:English
Published: Nature Publishing Group 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804166/
id pubmed-4804166
recordtype oai_dc
spelling pubmed-48041662016-03-25 Different states of synaptotagmin regulate evoked versus spontaneous release Bai, Hua Xue, Renhao Bao, Huan Zhang, Leili Yethiraj, Arun Cui, Qiang Chapman, Edwin R. Article 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. Nature Publishing Group 2016-03-22 /pmc/articles/PMC4804166/ /pubmed/27001899 http://dx.doi.org/10.1038/ncomms10971 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Bai, Hua
Xue, Renhao
Bao, Huan
Zhang, Leili
Yethiraj, Arun
Cui, Qiang
Chapman, Edwin R.
spellingShingle Bai, Hua
Xue, Renhao
Bao, Huan
Zhang, Leili
Yethiraj, Arun
Cui, Qiang
Chapman, Edwin R.
Different states of synaptotagmin regulate evoked versus spontaneous release
author_facet Bai, Hua
Xue, Renhao
Bao, Huan
Zhang, Leili
Yethiraj, Arun
Cui, Qiang
Chapman, Edwin R.
author_sort Bai, Hua
title Different states of synaptotagmin regulate evoked versus spontaneous release
title_short Different states of synaptotagmin regulate evoked versus spontaneous release
title_full Different states of synaptotagmin regulate evoked versus spontaneous release
title_fullStr Different states of synaptotagmin regulate evoked versus spontaneous release
title_full_unstemmed Different states of synaptotagmin regulate evoked versus spontaneous release
title_sort different states of synaptotagmin regulate evoked versus spontaneous release
description 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.
publisher Nature Publishing Group
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804166/
_version_ 1613556590643773440

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