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* Researchers found that synaptotagmin-1 binds to PtdIns(4,5)P through a lysine patch in its C2B domain, which may aid in preparing synaptic vesicles for fusion.
* The presence of calcium ions enhances synaptotagmin-1's interaction with the membrane, promoting its membrane penetration and prolonging
Article 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.
