title: Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor.
abstract: AP-3 is a member of the adaptor protein (AP) complex family that regulates the vesicular transport of cargo proteins in the secretory and endocytic pathways. There are two isoforms of AP-3: the ubiquitously expressed AP-3A and the neuron-specific AP-3B. Although the physiological role of AP-3A has recently been elucidated, that of AP-3B remains unsolved. To address this question, we generated mice lacking mu3B, a subunit of AP-3B. mu3B-/- mice suffered from spontaneous epileptic seizures. Morphological abnormalities were observed at synapses in these mice. Biochemical studies demonstrated the impairment of gamma-aminobutyric acid (GABA) release because of, at least in part, the reduction of vesicular GABA transporter in mu3B-/- mice. This facilitated the induction of long-term potentiation in the hippocampus and the abnormal propagation of neuronal excitability via the temporoammonic pathway. Thus, AP-3B plays a critical role in the normal formation and function of a subset of synaptic vesicles. This work adds a new aspect to the pathogenesis of epilepsy.
authors.affiliation: RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan.
authors.forename: Fubito
authors.initials: F
authors.lastname: Nakatsu
authors.forename: Motohiro
authors.initials: M
authors.lastname: Okada
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Mori
authors.forename: Noriko
authors.initials: N
authors.lastname: Kumazawa
authors.forename: Hiroto
authors.initials: H
authors.lastname: Iwasa
authors.forename: Gang
authors.initials: G
authors.lastname: Zhu
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kasagi
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Kamiya
authors.forename: Akihiro
authors.initials: A
authors.lastname: Harada
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishimura
authors.forename: Arata
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yuasa
authors.forename: Toshiya
authors.initials: T
authors.lastname: Manabe
authors.forename: Koichi
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohno
mesh_terms: D033963:Adaptor Protein Complex 3; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002966:Clathrin / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D004594:Electrophysiology; D050485:GABA Plasma Membrane Transport Proteins; D005838:Genotype; D005971:Glutamates / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D026901:Membrane Transport Proteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008954:Models, Biological; D008957:Models, Genetic; D018377:Neurotransmitter Agents; D020033:Protein Isoforms; D011995:Recombination, Genetic; D012640:Seizures; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
chemical_list: D033963:Adaptor Protein Complex 3; D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; D004268:DNA-Binding Proteins; D050485:GABA Plasma Membrane Transport Proteins; D005971:Glutamates; D026901:Membrane Transport Proteins; D018377:Neurotransmitter Agents; D020033:Protein Isoforms; D014157:Transcription Factors