Dynamic regulation of RGS2 suggests a novel mechanism in G-protein signaling and neuronal plasticity.
Long-term neuronal plasticity is known to be dependent on rapid de novo synthesis of mRNA and protein, and recent studies provide insight into the molecules involved in this response. Here, we demonstrate that mRNA encoding a member of the regulator of G-protein signaling (RGS) family, RGS2, is rapidly induced in neurons of the hippocampus, cortex, and striatum in response to stimuli that evoke plasticity. Although several members of the RGS family are expressed in brain with discrete neuronal localizations, RGS2 appears unique in that its expression is dynamically responsive to neuronal activity. In biochemical assays, RGS2 stimulates the GTPase activity of the alpha subunit of Gq and Gi1. The effect on Gi1 was observed only after reconstitution of the protein in phospholipid vesicles containing M2 muscarinic acetylcholine receptors. RGS2 also inhibits both Gq- and Gi-dependent responses in transfected cells. These studies suggest a novel mechanism linking neuronal activity and signal transduction.
Ingi
T
T
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21210, USA.
Krumins
A M
AM
Chidiac
P
P
Brothers
G M
GM
Chung
S
S
Snow
B E
BE
Barnes
C A
CA
Lanahan
A A
AA
Siderovski
D P
DP
Ross
E M
EM
Gilman
A G
AG
Worley
P F
PF
D000818:Animals; D019556:COS Cells / Q000737:chemistry / Q000201:enzymology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D003042:Cocaine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D017781:Genes, Immediate-Early / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D006868:Hydrolysis; D050356:Lipid Metabolism; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D003042:Cocaine; D006220:Haloperidol