title: Overlapping role of dynamin isoforms in synaptic vesicle endocytosis.
abstract: The existence of neuron-specific endocytic protein isoforms raises questions about their importance for specialized neuronal functions. Dynamin, a GTPase implicated in the fission reaction of endocytosis, is encoded by three genes, two of which, dynamin 1 and 3, are highly expressed in neurons. We show that dynamin 3, thought to play a predominantly postsynaptic role, has a major presynaptic function. Although lack of dynamin 3 does not produce an overt phenotype in mice, it worsens the dynamin 1 KO phenotype, leading to perinatal lethality and a more severe defect in activity-dependent synaptic vesicle endocytosis. Thus, dynamin 1 and 3, which together account for the overwhelming majority of brain dynamin, cooperate in supporting optimal rates of synaptic vesicle endocytosis. Persistence of synaptic transmission in their absence indicates that if dynamin plays essential functions in neurons, such functions can be achieved by the very low levels of dynamin 2.
authors.affiliation: Department of Cell Biology, HHMI, Program in Cellular Neuroscience, Neurodegeneration and Repair and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Raimondi
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Ferguson
authors.forename: Xuelin
authors.initials: X
authors.lastname: Lou
authors.forename: Moritz
authors.initials: M
authors.lastname: Armbruster
authors.forename: Summer
authors.initials: S
authors.lastname: Paradise
authors.forename: Silvia
authors.initials: S
authors.lastname: Giovedi
authors.forename: Mirko
authors.initials: M
authors.lastname: Messa
authors.forename: Nao
authors.initials: N
authors.lastname: Kono
authors.forename: Junko
authors.initials: J
authors.lastname: Takasaki
authors.forename: Valentina
authors.initials: V
authors.lastname: Cappello
authors.forename: Eileen
authors.initials: E
authors.lastname: O'Toole
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Ryan
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D034284:Dynamin I / Q000235:genetics / Q000378:metabolism*; D034286:Dynamin III / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D020033:Protein Isoforms; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D034284:Dynamin I; D034286:Dynamin III