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.

[1]  R. Malinow,et al.  Ras and Rap Control AMPA Receptor Trafficking during Synaptic Plasticity , 2002, Cell.

[2]  T. Akiyama,et al.  SPAL, a Rap‐specific GTPase activating protein, is present in the NMDA receptor‐PSD‐95 complex in the hippocampus , 2002, Genes to cells : devoted to molecular & cellular mechanisms.

[3]  Alcino J. Silva,et al.  Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1 , 2002, Nature.

[4]  J. Bos,et al.  Rap1 signalling: adhering to new models , 2001, Nature Reviews Molecular Cell Biology.

[5]  I. Komuro,et al.  Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase. , 2001, Journal of cell science.

[6]  T. Jacks,et al.  NF1 Tumor Suppressor Gene Function Narrowing the GAP , 2001, Cell.

[7]  Y. Yoneda,et al.  Molecular mechanisms associated with long-term consolidation of the NMDA signals. , 2000, Life sciences.

[8]  M. Katsuki,et al.  Regulation of Long-Term Potentiation by H-Ras through NMDA Receptor Phosphorylation , 2000, The Journal of Neuroscience.

[9]  R. Malinow,et al.  Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. , 2000, Science.

[10]  G M Edelman,et al.  A 9-nt segment of a cellular mRNA can function as an internal ribosome entry site (IRES) and when present in linked multiple copies greatly enhances IRES activity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[11]  M. Kennedy,et al.  A Synaptic Ras-GTPase Activating Protein (p135 SynGAP) Inhibited by CaM Kinase II , 1998, Neuron.

[12]  R. Huganir,et al.  SynGAP: a Synaptic RasGAP that Associates with the PSD-95/SAP90 Protein Family , 1998, Neuron.

[13]  S. Grant,et al.  A role for the Ras signalling pathway in synaptic transmission and long-term memory , 1997, Nature.

[14]  G Tocco,et al.  Glycine-induced long-term potentiation is associated with structural and functional modifications of alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptors. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Paul W. Frankland,et al.  A mouse model for the learning and memory deficits associated with neurofibromatosis type I , 1997, Nature Genetics.

[16]  D. Muller,et al.  A simple method for organotypic cultures of nervous tissue , 1991, Journal of Neuroscience Methods.

[17]  H. Kitayama,et al.  Genetic analysis of the Kirsten-ras-revertant 1 gene: potentiation of its tumor suppressor activity by specific point mutations. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Y. Takai,et al.  Tissue and subcellular distributions of the smg-21/rap1/Krev-1 proteins which are partly distinct from those of c-ras p21s , 1990, Molecular and cellular biology.

[19]  H. Kitayama,et al.  A ras-related gene with transformation suppressor activity , 1989, Cell.

[20]  M. Wigler,et al.  Purification and characterization of human H-ras proteins expressed in Escherichia coli , 1985, Molecular and cellular biology.