title: Epsin1 modulates synaptic vesicle retrieval capacity at CNS synapses.
abstract: Synaptic vesicle retrieval is an essential process for continuous maintenance of neural information flow after synaptic transmission. Epsin1, originally identified as an EPS15-interacting protein, is a major component of clathrin-mediated endocytosis. However, the role of Epsin1 in synaptic vesicle endocytosis at CNS synapses remains elusive. Here, we showed significantly altered synaptic vesicle endocytosis in neurons transfected with shRNA targeting Epsin1 during/after neural activity. Endocytosis was effectively restored by introducing shRNA-insensitive Epsin1 into Epsin1-depleted neurons. Domain studies performed on neurons in which domain deletion mutants of Epsin1 were introduced after Epsin1 knockdown revealed that ENTH, CLAP, and NPFs are essential for synaptic vesicle endocytosis, whereas UIMs are not. Strikingly, the efficacy of the rate of synaptic vesicle retrieval (the "endocytic capacity") was significantly decreased in the absence of Epsin1. Thus, Epsin1 is required for proper synaptic vesicle retrieval and modulates the endocytic capacity of synaptic vesicles.
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, South Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Kyung
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, South Korea.
authors.forename: Jae Ryul
authors.initials: JR
authors.lastname: Bae
authors.affiliation: Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, 15588 South Korea.
authors.forename: Dae-Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: School of Life Science, Bio Imaging and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju 61005 South Korea.
authors.forename: Woo Keun
authors.initials: WK
authors.lastname: Song
authors.affiliation: Department of Physiology, Kyung Hee University, School of Medicine, Seoul 02447, South Korea.|Neurodegeneration Control Research Center, Seoul, 02447, South Korea.
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004705:Endocytosis; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D000072417:Protein Domains; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D051272:Glucose Transporter Type 1; D034741:RNA, Small Interfering; C495679:Slc2a1 protein, rat; D016708:Synaptophysin; C494706:Vamp2 protein, rat; D050988:Vesicle-Associated Membrane Protein 2; C114154:epsin