title: Ca(2+) influx inhibits dynamin and arrests synaptic vesicle endocytosis at the active zone.
abstract: Ca(2+) entry into nerve terminals through clusters of voltage-dependent Ca(2+) channels (VDCCs) at active zones creates a microdomain of elevated intracellular free Ca(2+) concentration ([Ca(2+)](i)) that stimulates exocytosis. We show that this VDCC-mediated [Ca(2+)](i) elevation 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 Ca(2+) chelators. The Ca(2+)-dependent inhibition of endocytosis is mimicked in vitro by a low-affinity inhibition of dynamin I vesiculation of phospholipids. Increased [Ca(2+)](i) also inhibits dynamin II GTPase activity and receptor-mediated endocytosis in non-neuronal cells. VDCC-meditated Ca(2+) 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.
authors.affiliation: Cell Signaling Unit, Children's Medical Research Institute, Wentworthville 2145, Sydney, New South Wales, Australia. mcousin@cmri.usyd.edu.au
authors.forename: M A
authors.initials: MA
authors.lastname: Cousin
authors.forename: P J
authors.initials: PJ
authors.lastname: Robinson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D034284:Dynamin I; D034281:Dynamins; D004705:Endocytosis / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors* / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism; D009411:Nerve Endings / Q000502:physiology; D009994:Osmolar Concentration; D010743:Phospholipids / Q000502:physiology; D051381:Rats; D013572:Synaptic Vesicles / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D010743:Phospholipids; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034281:Dynamins; D002118:Calcium