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在有钙存在的情况下，磷脂酰肌醇磷酸（PtdInsP）和磷脂酰丝氨酸（PtdSer）协同作用，将突触结合蛋白-1捕获到质膜上。

PtdInsP and PtdSer cooperate to trap synaptotagmin-1 to the plasma membrane in the presence of calcium.

作者信息

Pérez-Lara Ángel, Thapa Anusa, Nyenhuis Sarah B, Nyenhuis David A, Halder Partho, Tietzel Michael, Tittmann Kai, Cafiso David S, Jahn Reinhard

机构信息

Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.

Department of Chemistry and Center for Membrane Biology, University of Virginia, Charlottesville, United States.

出版信息

Elife. 2016 Oct 28;5:e15886. doi: 10.7554/eLife.15886.

DOI:10.7554/eLife.15886
PMID:27791979
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5123861/
Abstract

The Ca-sensor synaptotagmin-1 that triggers neuronal exocytosis binds to negatively charged membrane lipids (mainly phosphatidylserine (PtdSer) and phosphoinositides (PtdIns)) but the molecular details of this process are not fully understood. Using quantitative thermodynamic, kinetic and structural methods, we show that synaptotagmin-1 (from and expressed in ) binds to PtdIns(4,5)P via a polybasic lysine patch in the C2B domain, which may promote the priming or docking of synaptic vesicles. Ca neutralizes the negative charges of the Ca-binding sites, resulting in the penetration of synaptotagmin-1 into the membrane, via binding of PtdSer, and an increase in the affinity of the polybasic lysine patch to phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P). These Ca-induced events decrease the dissociation rate of synaptotagmin-1 membrane binding while the association rate remains unchanged. We conclude that both membrane penetration and the increased residence time of synaptotagmin-1 at the plasma membrane are crucial for triggering exocytotic membrane fusion.

摘要

触发神经元胞吐作用的钙传感器突触结合蛋白-1与带负电荷的膜脂（主要是磷脂酰丝氨酸（PtdSer）和磷酸肌醇（PtdIns））结合，但其具体分子机制尚未完全清楚。通过定量热力学、动力学和结构方法，我们发现突触结合蛋白-1（来自并在中表达）通过C2B结构域中的多碱性赖氨酸区域与PtdIns(4,5)P结合，这可能促进突触小泡的启动或对接。钙离子中和了钙结合位点的负电荷，导致突触结合蛋白-1通过与PtdSer结合而穿透膜，并增加了多碱性赖氨酸区域与磷脂酰肌醇-4,5-二磷酸（PtdIns(4,5)P）的亲和力。这些钙离子诱导的事件降低了突触结合蛋白-1与膜结合的解离速率，而结合速率保持不变。我们得出结论，膜穿透以及突触结合蛋白-1在质膜上停留时间的增加对于触发胞吐性膜融合至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/8bce3dd5198a/elife-15886-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/a147202534f5/elife-15886-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/7b87f1e23367/elife-15886-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/c8668ae2e423/elife-15886-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/0af8f4ccad05/elife-15886-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/6e858d6299c9/elife-15886-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/dcb6ca6ac8e2/elife-15886-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/5c1d84edd927/elife-15886-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/8bce3dd5198a/elife-15886-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/a147202534f5/elife-15886-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/020d50cf5b12/elife-15886-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/71de1aa4b0d7/elife-15886-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/de800698fce8/elife-15886-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/7b87f1e23367/elife-15886-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/c8668ae2e423/elife-15886-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/0af8f4ccad05/elife-15886-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/6e858d6299c9/elife-15886-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/dcb6ca6ac8e2/elife-15886-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/5c1d84edd927/elife-15886-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cb9/5123861/8bce3dd5198a/elife-15886-fig7.jpg

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