PtdInsP2 and PtdSer cooperate to trap synaptotagmin-1 to the plasma membrane in the presence of calcium

eLife

Sarah B Nyenhuis¹  David S Cafiso¹  Anusa Thapa¹  David A Nyenhuis¹  Michael Tietzel²  Kai Tittmann²  Reinhard Jahn³  Ángel Pérez-Lara³  Partho Halder³ 

[1] Department of Chemistry and Center for Membrane Biology, University of Virginia, Charlottesville, United States;Department of Molecular Enzymology, Göttingen Center for Molecular Biosciences, Georg-August University Göttingen, Göttingen, Germany;Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany;

关键词: exocytosis;    synaptotagmin;    kinetics;    thermodynamics;   

DOI  :  10.7554/eLife.15886

来源: DOAJ

【 摘 要 】

The Ca2+-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 Rattus norvegicus and expressed in Escherichia coli) binds to PtdIns(4,5)P2 via a polybasic lysine patch in the C2B domain, which may promote the priming or docking of synaptic vesicles. Ca2+ neutralizes the negative charges of the Ca2+-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)P2). These Ca2+-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.

【 授权许可】

Unknown