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Norway

PMID:15492041  

Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor.

Fubito Nakatsu | Motohiro Okada | Fumiaki Mori | Noriko Kumazawa | Hiroto Iwasa | Gang Zhu | Yasufumi Kasagi | Haruyuki Kamiya | Akihiro Harada | Kazuhiro Nishimura | Arata Takeuchi | Taisuke Miyazaki | Masahiko Watanabe | Shigeki Yuasa | Toshiya Manabe | Koichi Wakabayashi | Sunao Kaneko | Takashi Saito | Hiroshi Ohno
The Journal of cell biology | 2004

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.

Pubmed ID: 15492041

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pClamp (tool)

RRID:SCR_011323

Software suite for electrophysiology data acquisition and analysis by Molecular Devices. Used for the control and recording of voltage clamp, current clamp, and patch clamp experiments. The software suite consists of Clampex 11 Software for data acquisition, AxoScope 11 Software for background recording, Clampfit 11 Software for data analysis, and optional Clampfit Advanced Analysis Module for sophisticated and streamlined analysis.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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