title: Ca(2+) and calmodulin initiate all forms of endocytosis during depolarization at a nerve terminal.
abstract: Although endocytosis maintains synaptic transmission, how endocytosis is initiated is unclear. We found that calcium influx initiated all forms of endocytosis at a single nerve terminal in rodents, including clathrin-dependent slow endocytosis, bulk endocytosis, rapid endocytosis and endocytosis overshoot (excess endocytosis), with each being evoked with a correspondingly higher calcium threshold. As calcium influx increased, endocytosis gradually switched from very slow endocytosis to slow endocytosis to bulk endocytosis to rapid endocytosis and to endocytosis overshoot. The calcium-induced endocytosis rate increase was a result of the speeding up of membrane invagination and fission. Pharmacological experiments suggested that the calcium sensor mediating these forms of endocytosis is calmodulin. In addition to its role in recycling vesicles, calcium/calmodulin-initiated endocytosis facilitated vesicle mobilization to the readily releasable pool, probably by clearing fused vesicle membrane at release sites. Our findings provide a unifying mechanism for the initiation of various forms of endocytosis that are critical in maintaining exocytosis.
authors.affiliation: National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
authors.forename: Xin-Sheng
authors.initials: XS
authors.lastname: Wu
authors.affiliation: National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: McNeil
authors.affiliation: National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xu
authors.affiliation: National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
authors.forename: Junmei
authors.initials: J
authors.lastname: Fan
authors.affiliation: National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Pulmonary Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ernestina
authors.initials: E
authors.lastname: Melicoff
authors.affiliation: Department of Pulmonary Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Adachi
authors.affiliation: National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.affiliation: National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
authors.forename: Ling-Gang
authors.initials: LG
authors.lastname: Wu
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002147:Calmodulin / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors
chemical_list: D002147:Calmodulin; D002118:Calcium