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Neuronal Nogo‐A regulates glutamate receptor subunit expression in hippocampal neurons
Author(s) -
Peng Xiangmin,
Kim Jeeyong,
Zhou Zhigang,
Fink David J.,
Mata Marina
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07520.x
Subject(s) - hippocampal formation , glutamate receptor , neuroscience , protein subunit , hippocampus , receptor , microbiology and biotechnology , nmda receptor , chemistry , biology , biochemistry , gene
J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07520.x 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.