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J Cell Biol. 2004 Oct 25;167(2):293-302. Epub 2004 Oct 18.

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

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  • 1RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan.

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.

PMID:
15492041
[PubMed - indexed for MEDLINE]
PMCID:
PMC2172536
Free PMC Article

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