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Vol. 12, Issue 5, 1421-1430, May 2001

Role of Rab3 GDP/GTP Exchange Protein in Synaptic Vesicle Trafficking at the Mouse Neuromuscular Junction

Miki Tanaka,*Dagger Jun Miyoshi,*Dagger Hiroyoshi Ishizaki,* Atsushi Togawa,* Katsunori Ohnishi,§ Katsuaki Endo,§ Kaho Matsubara,|| Akira Mizoguchi,|| Takashi Nagano, Makoto Sato, Takuya Sasaki,#** and Yoshimi Takai#dagger dagger

 *Takai Biotimer Project, dagger Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Corporation, c/o JCR Pharmaceuticals Co., Ltd., Kobe 651-2241, Japan; Departments of  §Physiology and  ||Anatomy and Neurobiology, Kyoto University Graduate School of Medicine/Faculty of Medicine, Kyoto 606-8501, Japan;  Department of Anatomy (2), Faculty of Medicine, Fukui Medical University, Fukui 910-1193, Japan; and  #Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Osaka 565-0871, Japan

The Rab3 small G protein family consists of four members, Rab3A, -3B, -3C, and -3D. Of these members, Rab3A regulates Ca2+-dependent neurotransmitter release. These small G proteins are activated by Rab3 GDP/GTP exchange protein (Rab3 GEP). To determine the function of Rab3 GEP during neurotransmitter release, we have knocked out Rab3 GEP in mice. Rab3 GEP-/- mice developed normally but died immediately after birth. Embryos at E18.5 showed no evoked action potentials of the diaphragm and gastrocnemius muscles in response to electrical stimulation of the phrenic and sciatic nerves, respectively. In contrast, axonal conduction of the spinal cord and the phrenic nerve was not impaired. Total numbers of synaptic vesicles, especially those docked at the presynaptic plasma membrane, were reduced at the neuromuscular junction ~10-fold compared with controls, whereas postsynaptic structures and functions appeared normal. Thus, Rab3 GEP is essential for neurotransmitter release and probably for formation and trafficking of the synaptic vesicles.

dagger dagger Corresponding author. E-mail address: ytakai{at}molbio.med.osaka-u.ac.jp.

Present addresses: Dagger Department of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan; ** Department of Biochemistry, The University of Tokushima School of Medicine, Tokushima 770-8503, Japan.

Molecular Biology of the Cell
Vol. 12, 1421-1430, May 2001
Copyright © 2001 by The American Society for Cell Biology


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