title: Neuronal Nogo-A regulates glutamate receptor subunit expression in hippocampal neurons.
abstract: Nogo-A and its cognate receptor NogoR1 (NgR1) are both expressed in neurons. To explore the function of these proteins in neurons of the CNS, we carried out a series of studies using postnatal hippocampal neurons in culture. Interfering with the binding of Nogo-A to NgR1 either by adding truncated soluble fragment of NgR1 (NgSR) or by reducing NgR1 protein with a specific siRNA, resulted in a marked reduction in Nogo-A expression. Inhibition of Rho-ROCK or MEK-MAPK signaling resulted in a similar reduction in neuronal Nogo-A mRNA and protein. Reducing Nogo-A protein levels by siRNA resulted in an increase in the post-synaptic scaffolding protein PSD95, as well as increases in GluA1/GluA2 AMPA receptor and GluN1/GluN2A/GluN2B NMDA glutamate receptor subunits. siRNA treatment to reduce Nogo-A resulted in phosphorylation of mTOR; addition of rapamycin to block mTOR signaling prevented the up-regulation in glutamate receptor subunits. siRNA reduction of NgR1 resulted in increased expression of the same glutamate receptor subunits. Taken together the results suggest that transcription and translation of Nogo-A in hippocampal neurons is regulated by a signaling through NgR1, and that interactions between neuronal Nogo-A and NgR1 regulate glutamatergic transmission by altering NMDA and AMPA receptor levels through an rapamycin-sensitive mTOR-dependent translation mechanism.
authors: Department of Neurology, University of Michigan and VA Ann Arbor Healthcare System, Ann Arbor, Michigan 48109, USA.
authors: Xiangmin
authors: X
authors: Peng
authors: Jeeyong
authors: J
authors: Kim
authors: Zhigang
authors: Z
authors: Zhou
authors: David J
authors: DJ
authors: Fink
authors: Marina
authors: M
authors: Mata
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D009185:Myelin Proteins / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000070798:Nogo Proteins; D011247:Pregnancy; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014162:Transfection; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; D021122:Protein Subunits; D034741:RNA, Small Interfering; D017470:Receptors, Glutamate; C000603197:Rtn4 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D049452:Green Fluorescent Proteins; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020558:GTP Phosphohydrolases; D020123:Sirolimus