Metabotropic glutamate receptors trigger postsynaptic protein synthesis.
K+ depolarization or addition of glutamate to a synaptoneurosome preparation triggers a rapid increase in size of polyribosomal aggregates isolated by centrifugation of lysate through 1 M sucrose. The profile of response to the glutamate analogues quisqualate, ibotenate, and 1-aminocyclopentane-1,3-dicarboxylate corresponds to that of metabotropic receptors. Glutamate stimulation is mimicked by the diacylglycerol analogue 1-oleoyl-2-acetylglycerol and by the protein kinase C activator phorbol dibutyrate. The phospholipase blockers 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate and quinacrine reduce the late phase of the response. The protein kinase C inhibitor calphostin C suppresses the response to 1-aminocyclopentane-1,3-dicarboxylate. These data indicate that glutamatergic synapses upregulate postsynaptic protein synthesis via metabotropic glutamate receptors coupled to the phosphatidylinositol second-messenger system. This mechanism could underlie the reported involvement of metabotropic glutamate receptors in long-term potentiation and other forms of neural plasticity.
Weiler
I J
IJ
Department of Psychology, University of Illinois, Urbana-Champaign 61801.
Greenough
W T
WT
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D010716:Phosphatidylinositols / Q000378:metabolism; D011132:Polyribosomes / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*; D013570:Synaptic Membranes / Q000502:physiology
D005971:Glutamates; D009419:Nerve Tissue Proteins; D010716:Phosphatidylinositols; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D011493:Protein Kinase C; D011188:Potassium; D002118:Calcium