Possible involvement of Rap1 and Ras in glutamatergic synaptic transmission.
Rap1A, first identified as a suppressor of transformed phenotype induced by an activated ras oncogene, is abundantly expressed in the brain. Its neurophysiological function, however, is poorly understood. When an activated Rap1A mutant (Rap1-12V) or a dominant negative H-Ras mutant (Ras-17N) was expressed in CA1 neurons in cultured hippocampal slices using the sindbis virus-mediated gene transfer technique, NMDA receptor current in response to Schaffer collateral stimulation was suppressed. Expression of activated H-Ras mutant (Ras-12V) resulted in the elevation of both NMDA receptor current and AMPA receptor current. These results implicate counteracting functions of Ras and Rap1 in the regulation of NMDA receptor-mediated synaptic transmission and a positive regulatory role of Ras in AMPA receptor-mediated synaptic transmission.
Imamura
Y
Y
Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. yimamura@libra.ls.m-kagaku.co.jp
Matsumoto
N
N
Kondo
S
S
Kitayama
H
H
Noda
M
M
D000818:Animals; D011905:Genes, ras / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D009154:Mutation / Q000502:physiology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D020827:rap1 GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D020827:rap1 GTP-Binding Proteins; D018631:ras Proteins