NMDA Receptor Phosphorylation at a Site Affected in Schizophrenia Controls Synaptic and Behavioral Plasticity

Li, B., Devidze, N., Barengolts, D., Prostak, N., Sphicas, E., Apicella, A. J., Malinow, R., Emamian, E. S. (September 2009) NMDA Receptor Phosphorylation at a Site Affected in Schizophrenia Controls Synaptic and Behavioral Plasticity. J Neurosci, 29 (38). pp. 11965-11972.

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Abstract

Phosphorylation of the NR1 subunit of NMDA receptors (NMDARs) at serine (S) 897 is markedly reduced in schizophrenia patients. However, the role of NR1 S897 phosphorylation in normal synaptic function and adaptive behaviors are unknown. To address these questions, we generated mice in which the NR1 S897 is replaced with alanine (A). This knock-in mutation causes severe impairment in NMDAR synaptic incorporation and NMDAR-mediated synaptic transmission. Furthermore, the phosphomutant animals have reduced AMPA receptor (AMPAR)-mediated synaptic transmission, decreased AMPAR GluR1 subunit in the synapse, and impaired long-term potentiation. Finally, the mutant mice exhibit behavioral deficits in social interaction and sensorimotor gating. Our results suggest that an impairment in NR1 phosphorylation leads to glutamatergic hypofunction that can contribute to behavioral deficits associated with psychiatric disorders.

Item Type:	Paper
Subjects:	diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics diseases & disorders > mental disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > NMDA receptor bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification diseases & disorders > mental disorders > schizophrenia organism description > animal behavior organism description > animal > mammal > primates > hominids > human bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
CSHL Authors:	Apicella, Alfonso J. Li, Bo Malinow, Roberto
Communities:	CSHL labs > Li lab CSHL labs > Malinow lab
Depositing User:	Matt Covey
Date:	23 September 2009
Date Deposited:	20 Feb 2013 16:06
Last Modified:	20 Feb 2013 16:06
PMCID:	PMC2804063
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/27426

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