Details

Autor(en) / Beteiligte

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

Titel

Defective Function of GABA-Containing Synaptic Vesicles in Mice Lacking the AP-3B Clathrin Adaptor

Ist Teil von

• The Journal of cell biology, 2004-10, Vol.167 (2), p.293-302

Ort / Verlag

United States: Rockefeller University Press

Erscheinungsjahr

2004

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 μ3B, a subunit of AP-3B. μ 3 B-/- mice suffered from spontaneous epileptic seizures. Morphological abnormalities were observed at synapses in these mice. Biochemical studies demonstrated the impairment of γ-aminobutyric acid (GABA) release because of, at least in part, the reduction of vesicular GABA transporter in μ 3 B-/- 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.