title: Fast neurotransmitter release regulated by the endocytic scaffold intersectin.
abstract: Sustained fast neurotransmission requires the rapid replenishment of release-ready synaptic vesicles (SVs) at presynaptic active zones. Although the machineries for exocytic fusion and for subsequent endocytic membrane retrieval have been well characterized, little is known about the mechanisms underlying the rapid recruitment of SVs to release sites. Here we show that the Down syndrome-associated endocytic scaffold protein intersectin 1 is a crucial factor for the recruitment of release-ready SVs. Genetic deletion of intersectin 1 expression or acute interference with intersectin function inhibited the replenishment of release-ready vesicles, resulting in short-term depression, without significantly affecting the rate of endocytic membrane retrieval. Acute perturbation experiments suggest that intersectin-mediated vesicle replenishment involves the association of intersectin with the fissioning enzyme dynamin and with the actin regulatory GTPase CDC42. Our data indicate a role for the endocytic scaffold intersectin in fast neurotransmitter release, which may be of prime importance for information processing in the brain.
authors: Graduate School of Brain Science, Doshisha University, Kyoto 6190225, Japan. tsakaba@mail.doshisha.ac.jp
authors: Takeshi
authors: T
authors: Sakaba
authors: Natalia L
authors: NL
authors: Kononenko
authors: Jelena
authors: J
authors: Bacetic
authors: Arndt
authors: A
authors: Pechstein
authors: Jan
authors: J
authors: Schmoranzer
authors: Lijun
authors: L
authors: Yao
authors: Holger
authors: H
authors: Barth
authors: Oleg
authors: O
authors: Shupliakov
authors: Oliver
authors: O
authors: Kobler
authors: Klaus
authors: K
authors: Aktories
authors: Volker
authors: V
authors: Haucke
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D001933:Brain Stem / Q000378:metabolism; D004705:Endocytosis; D017353:Gene Deletion; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D018377:Neurotransmitter Agents; D010455:Peptides; C115919:intersectin 1; D020764:cdc42 GTP-Binding Protein
keywords: endocytosis; synaptic transmission; synaptic vesicle recruitment
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