title: Dynamin isoforms decode action potential firing for synaptic vesicle recycling.
abstract: Presynaptic nerve terminals must maintain stable neurotransmission via synaptic vesicle membrane recycling despite encountering wide fluctuations in the number and frequency of incoming action potentials (APs). However, the molecular mechanism linking variation in neuronal activity to vesicle trafficking is unknown. Here, we combined genetic knockdown and direct physiological measurements of synaptic transmission from paired neurons to show that three isoforms of dynamin, an essential endocytic protein, work individually to match vesicle reuse pathways, having distinct rate and time constants with physiological AP frequencies. Dynamin 3 resupplied the readily releasable pool with slow kinetics independently of the AP frequency but acted quickly, within 20 ms of the incoming AP. Under high-frequency firing, dynamin 1 regulated recycling to the readily releasable pool with fast kinetics in a slower time window of greater than 50 ms. Dynamin 2 displayed a hybrid response between the other isoforms. Collectively, our findings show how dynamin isoforms select appropriate vesicle reuse pathways associated with specific neuronal firing patterns.
authors.affiliation: Department of Physiology, Tokyo Medical University, Tokyo 160-8402, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Tanifuji
authors.forename: Megumi
authors.initials: M
authors.lastname: Funakoshi-Tago
authors.forename: Fumihito
authors.initials: F
authors.lastname: Ueda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kasahara
authors.forename: Sumiko
authors.initials: S
authors.lastname: Mochida
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D034281:Dynamins / Q000502:physiology*; D004594:Electrophysiology; D004705:Endocytosis; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D009474:Neurons / Q000502:physiology; D016716:PC12 Cells; D017729:Presynaptic Terminals / Q000502:physiology; D020033:Protein Isoforms / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000502:physiology*
chemical_list: D020033:Protein Isoforms; D034281:Dynamins
keywords: Action Potential; Dynamin; Electrophysiology; Endocytosis; Membrane Trafficking; Neurobiology; Sympathetic Neuron; Synapses; Synaptic Vesicle; siRNA