Converging signal on ERK1/2 activity regulates group I mGluR-mediated Arc transcription.
The expression of Arc is tightly coupled to synaptic activities. Recent studies suggested the functional relevance of Arc translation in group I metabotropic glutamate receptor (mGluR)-mediated long-term depression. The present study investigated the transcription-dependent changes of Arc in response to the activation of group I mGluR by (R,S)-3,5-dihydroxyphenylglycine (DHPG) in cultured cortical neurons. The increase in Arc mRNA did not require de novo protein synthesis, indicating that Arc is an immediate early gene upon DHPG stimulation. We further examined the major pathways involved in group I mGluR signaling, and found that DHPG-induced Arc up-regulation depended on CaMK, PLC, and ERK1/2 activity. Moreover, the activity of NMDA receptors, but not l-type voltage gated calcium channels (l-VGCC), was required for Arc transcription. Interestingly, blocking CaMK, PLC, and NMDAR, but not l-VGCC, suppressed DHPG-stimulated ERK1/2 activation. These data suggest the central role of ERK1/2 in group I mGluR-mediated Arc transcription.
Wang
Yan
Y
Behavioral Genetics Center, Institute of Psychology, Chinese Academy of Science, Beijing 100101, PR China.
Zheng
Fei
F
Zhou
Xianju
X
Sun
Zhongsheng
Z
Wang
Hongbing
H
D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C092069:activity regulated cytoskeletal-associated protein; C104077:metabotropic glutamate receptor type 1; D008734:Methoxyhydroxyphenylglycol; C121465:6-methyl-2-(phenylethynyl)pyridine; D050882:CREB-Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases; C010117:3,4-dihydroxyphenylglycol