Circular Oligomerization is an Intrinsic Property of Synaptotagmin

Overview

Journal Elife

Specialty Biology

Date 2017 Aug 30

PMID 28850328

Citations 23

Authors

Jing Wang

Feng Li

Oscar D Bello

Charles Vaughn Sindelar

Frederic Pincet

Shyam S Krishnakumar

James E Rothman

Affiliations

Soon will be listed here.

Abstract

Previously, we showed that synaptotagmin1 (Syt1) forms Ca-sensitive ring-like oligomers on membranes containing acidic lipids and proposed a potential role in regulating neurotransmitter release (Zanetti et al., 2016). Here, we report that Syt1 assembles into similar ring-like oligomers in solution when triggered by naturally occurring polyphosphates (PIP2 and ATP) and magnesium ions (Mg). These soluble Syt1 rings were observed by electron microscopy and independently demonstrated and quantified using fluorescence correlation spectroscopy. Oligomerization is triggered when polyphosphates bind to the polylysine patch in C2B domain and is stabilized by Mg, which neutralizes the Ca-binding aspartic acids that likely contribute to the C2B interface in the oligomer. Overall, our data show that ring-like polymerization is an intrinsic property of Syt1 with reasonable affinity that can be triggered by the vesicle docking C2B-PIP2 interaction and raise the possibility that Syt1 rings could pre-form on the synaptic vesicle to facilitate docking.

Citing Articles

Quantitative single-molecule analysis of assembly and Ca-dependent disassembly of synaptotagmin oligomers on lipid bilayers.

Li F, Coleman J, Redondo-Morata L, Kalyana Sundaram R, Stroeva E, Rothman J Commun Biol. 2024; 7(1):1608.

PMID: 39627539 PMC: 11615320. DOI: 10.1038/s42003-024-07317-9.

Synaptotagmin-1 undergoes phase separation to regulate its calcium-sensitive oligomerization.

Zhu M, Xu H, Jin Y, Kong X, Xu B, Liu Y J Cell Biol. 2024; 223(10.

PMID: 38980206 PMC: 11232894. DOI: 10.1083/jcb.202311191.

Calcium Sensors of Neurotransmitter Release.

Zhou Q Adv Neurobiol. 2023; 33:119-138.

PMID: 37615865 DOI: 10.1007/978-3-031-34229-5_5.

Vesicle trafficking and vesicle fusion: mechanisms, biological functions, and their implications for potential disease therapy.

Cui L, Li H, Xi Y, Hu Q, Liu H, Fan J Mol Biomed. 2022; 3(1):29.

PMID: 36129576 PMC: 9492833. DOI: 10.1186/s43556-022-00090-3.

Synaptotagmin rings as high-sensitivity regulators of synaptic vesicle docking and fusion.

Zhu J, McDargh Z, Li F, Krishnakumar S, Rothman J, OShaughnessy B Proc Natl Acad Sci U S A. 2022; 119(38):e2208337119.

PMID: 36103579 PMC: 9499556. DOI: 10.1073/pnas.2208337119.

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