Ca2+Influx Inhibits Dynamin and Arrests Synaptic Vesicle Endocytosis at the Active Zone

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Abstract
Ca2+entry into nerve terminals through clusters of voltage-dependent Ca2+channels (VDCCs) at active zones creates a microdomain of elevated intracellular free Ca2+concentration ([Ca2+]i) that stimulates exocytosis. We show that this VDCC-mediated [Ca2+]ielevation has no specific role in stimulating endocytosis but can inhibit endocytosis evoked by three different methods in isolated mammalian nerve terminals. The inhibition can be relieved by using either VDCC antagonists or fast, but not slow, binding intracellular Ca2+chelators. The Ca2+-dependent inhibition of endocytosis is mimickedin vitroby a low-affinity inhibition of dynamin I vesiculation of phospholipids. Increased [Ca2+]ialso inhibits dynamin II GTPase activity and receptor-mediated endocytosis in non-neuronal cells. VDCC-meditated Ca2+entry inhibits dynamin-mediated endocytosis at the active zone and provides neurons with a mechanism to clear recycling vesicles to nonactive zone regions during periods of high activity.