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

被引:87
作者
Nakatsu, F
Okada, M
Mori, F
Kumazawa, N
Iwasa, H
Zhu, G
Kasagi, Y
Kamiya, H
Harada, A
Nishimura, K
Takeuchi, A
Miyazaki, T
Watanabe, M
Yuasa, S
Manabe, T
Wakabayashi, K
Kaneko, S
Saito, T
Ohno, H [1 ]
机构
[1] RIKEN, Res Ctr Allergy & Immunol, Kanagawa 2300045, Japan
[2] Kanazawa Univ, Inst Canc Res, Div Mol Membrane Biol, Kanazawa, Ishikawa 9200934, Japan
[3] Hirosaki Univ, Sch Med, Dept Neuropsychiat, Hirosaki, Aomori 0368216, Japan
[4] Hirosaki Univ, Sch Med, Dept Neuropsychiat, Hirosaki, Aomori 0368216, Japan
[5] Hirosaki Univ, Sch Med, Inst Brain Sci, Dept Neuropathol, Hirosaki, Aomori 0368562, Japan
[6] Univ Tokyo, Inst Med Sci, Dept Basic Med Sci, Div Neoronal Network, Tokyo 1088639, Japan
[7] Chiba Univ, Grad Sch Med, Dept Mol Genet, Chiba 2608670, Japan
[8] Chiba Univ, Grad Sch Med, Dept Integrat Neruophysiol, Chiba 2608670, Japan
[9] Kobe Univ, Fac Med, Dept Neurosci, Div Cell Biol & Neurophysiol, Kobe, Hyogo 6500017, Japan
[10] Gunma Univ, Dept Cell Biol, Lab Cellular & Mol Morphol, Inst Mol 7 Cellular Regulat, Gunma 3718512, Japan
[11] Chiba Univ, Grad Sch Pharmaceut Sci, Dept Clin Biochem, Chiba 2608675, Japan
[12] Hokkaido Univ, Sch Med, Dept Anat, Sapporo 0608638, Japan
[13] Natl Inst Neurosci, Dept Ultrastruct Res, Tokyo 1878502, Japan
关键词
D O I
10.1083/jcb.200405032
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
A P-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.
引用
收藏
页码:293 / 302
页数:10
相关论文
共 51 条
[41]   TRACE-METALS AND OTOLITH DEFECTS IN MOCHA MICE [J].
ROLFSEN, RM ;
ERWAY, LC .
JOURNAL OF HEREDITY, 1984, 75 (03) :158-162
[42]   A transgenic mouse line that retains Cre recombinase activity in mature oocytes irrespective of the cre transgene transmission [J].
Sakai, K ;
Miyazaki, J .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 237 (02) :318-324
[43]   REPORT OF IFCN COMMITTEE ON CLINICAL RELEVANCE OF KINDLING - KINDLING - BASIC MECHANISMS AND CLINICAL VALIDITY [J].
SATO, M ;
RACINE, RJ ;
MCINTYRE, DC .
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY, 1990, 76 (05) :459-472
[44]   RIM1α forms a protein scaffold for regulating neurotransmitter release at the active zone [J].
Schoch, S ;
Castillo, PE ;
Jo, T ;
Mukherjee, K ;
Geppert, M ;
Wang, Y ;
Schmitz, F ;
Malenka, RC ;
Südhof, TC .
NATURE, 2002, 415 (6869) :321-326
[45]   Abnormal vesicular trafficking in mouse models of Hermansky-Pudlak syndrome [J].
Swank, RT ;
Novak, EK ;
McGarry, MP ;
Zhang, YK ;
Li, W ;
Zhang, Q ;
Feng, LJ .
PIGMENT CELL RESEARCH, 2000, 13 :59-67
[46]   EATING DISORDER AND EPILEPSY IN MICE LACKING 5-HT2C SEROTONIN RECEPTORS [J].
TECOTT, LH ;
SUN, LM ;
AKANA, SF ;
STRACK, AM ;
LOWENSTEIN, DH ;
DALLMAN, MF ;
JULIUS, D .
NATURE, 1995, 374 (6522) :542-546
[47]   Impairment of inhibitory synaptic transmission in mice lacking synapsin I [J].
Terada, S ;
Tsujimoto, T ;
Takei, Y ;
Takahashi, T ;
Hirokawa, N .
JOURNAL OF CELL BIOLOGY, 1999, 145 (05) :1039-1048
[48]   Simultaneous multi-site recordings of neural activity with an inline multi-electrode array and optical measurement in rat hippocampal slices [J].
Tominaga, T ;
Tominaga, Y ;
Ichikawa, M .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2001, 443 (02) :317-322
[49]   FACILITATED INDUCTION OF HIPPOCAMPAL LONG-LASTING POTENTIATION DURING BLOCKADE OF INHIBITION [J].
WIGSTROM, H ;
GUSTAFSSON, B .
NATURE, 1983, 301 (5901) :603-604
[50]   NMDA receptor subunits GluRε1, GluRε3 and GluRζ1 are enriched at the mossy fibre-granule cell synapse in the adult mouse cerebellum [J].
Yamada, K ;
Fukaya, M ;
Shimizu, H ;
Sakimura, K ;
Watanabe, M .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2001, 13 (11) :2025-2036