• Xiangmin Peng, Jeeyong Kim, Zhigang Zhou, David J Fink, and Marina Mata.
• Department of Neurology, University of Michigan and VA Ann Arbor Healthcare System, Ann Arbor, Michigan 48109, USA.
• J. Neurochem. 2011 Dec 1;119(6):1183-93.

AbstractNogo-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.© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

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