EFFECT OF CALCIUM ION ON SYNAPTOTAGMIN-LIKE PROTEIN DURING PRE-FUSION OF VESICLE FOR EXOCYTOSIS IN BLOOD-BRAIN BARRIER

Effect of Calcium ion on synaptotagmin-like protein during pre-fusion of vesicle for exocytosis in blood-brain barrier

Effect of Calcium ion on synaptotagmin-like protein during pre-fusion of vesicle for exocytosis in blood-brain barrier

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Background: Calcium signaling and membrane fusion play key roles in exocytosis of drug-containing vesicles through Commercial Vacuum Cleaner the blood-brain barrier (BBB).Identifying the role of synaptotagmin-like protein4-a (Slp4-a) in the presence of Ca2+ ions, at the pre-fusion stage of a vesicle with the basolateral membrane of endothelial cell, can reveal brain drug transportation across BBB.Methods: We utilized molecular dynamics (MD) simulations with a coarse-grained PACE force field to investigate the behaviors of Slp4-a with vesicular and endothelial membranes at the pre-fusion stage of exocytosis since all-atom MD simulation or experiments are more time-consuming and expensive to capture these behaviors.Results: The Slp4-a pulls lipid membranes (vesicular and endothelial) into close proximity and disorganizes lipid arrangement at contact points, which are predictors for initiation of fusion.

Our MD results also indicate that Slp4-a needs Ca2+ to bind with weakly-charged POPE lipids (phosphatidylethanolamine).Conclusions: Slp4-a is LADIES PANTS SUIT an important trigger for membrane fusion in BBB exocytosis.It binds to lipid membranes at multiple binding sites and triggers membrane disruption for fusion in calcium-dependent case.General significance: Understanding the prefusion process of the vesicle will help to design better drug delivery mechanisms to the brain through formidable BBB.

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