Glutamate-stimulated calcium activation of Ras/Erk pathway mediated by nitric oxide.
NMDA-type glutamate receptor-mediated increases in intracellular calcium play a critical role in synaptic plasticity involved in learning and memory. Calcium-dependent activation of Ras and extracellular signal-regulated kineses (Erks) may transmit the glutamate signal to the nucleus which is ultimately important for long-lasting neuronal responses. The mechanism by which changes in cytoplasmic calcium mediate NMDA-induced activation of Ras and Erk is not known. In cerebral cortical neurons, this calcium influx through NMDA receptors activates Ras and its downstream effector, Erk, via nitric oxide (NO) generation by calcium-dependent neuronal NO synthase. We propose that NO is a key link between NMDA-mediated increases in cytoplasmic calcium and activity-dependent long-term changes such as differentiation, survival and synaptic plasticity.
Yun
H Y
HY
Department of Biochemistry, Chung-Ang University, College of Medicine, Seoul, South Korea. hyyun@cau.ac.kr
Dawson
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VL
Dawson
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TM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016202:N-Methylaspartate / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000502:physiology*; D018631:ras Proteins / Q000378:metabolism*
D020030:Nitric Oxide Donors; D017470:Receptors, Glutamate; D009569:Nitric Oxide; D018698:Glutamic Acid; D016202:N-Methylaspartate; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester