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Published April 26, 1994 | Published
Journal Article Open

The major tyrosine-phosphorylated protein in the postsynaptic density fraction is N-methyl-D-aspartate receptor subunit 2B


The postsynaptic density (PSD) is a specialization of the submembranous cytoskeleton that is visible in the electron microscope on the cytoplasmic face of the postsynaptic membrane. A subcellular fraction enriched in structures with the morphology of PSDs contains signal-transduction molecules thought to regulate receptor localization and function in the central nervous system. We have purified a prominent tyrosine-phosphorylated glycoprotein of apparent molecular mass 180 kDa, termed PSD-gp180, that is highly enriched in the rat forebrain PSD fraction. The sequences of four tryptic peptides generated from the protein reveal that it is the 2B subunit of the N-methyl-D-aspartate (NMDA) type glutamate receptor. We have confirmed the identity of PSD-gp180 by showing that it reacts with antibodies raised against a unique fragment of the 2B subunit of the NMDA receptor. We also show that the 2B subunit is the most prominently tyrosine-phosphorylated protein in the PSD fraction based upon recognition by an anti-phosphotyrosine antibody. Two types of NMDA receptor subunits have been identified by molecular cloning [Nakanishi, S. (1992) Science 258, 597-603]. The single type 1 subunit is expressed throughout the brain and is necessary for formation of the receptor channel. The four type 2 subunits (2A, 2B, 2C, and 2D) are expressed in discrete brain regions, contain unusually long unique C termini, and confer distinct kinetic properties on NMDA receptors that contain them. Our findings suggest that, in the forebrain, NMDA receptor subunit 2B may serve to anchor NMDA receptors at the postsynaptic membrane through its interaction with the PSD. The prominent presence of tyrosine phosphate further suggests that the NMDA receptor may be regulated by tyrosine phosphorylation or that it may participate in signaling through tyrosine phosphorylation and through its ion channel.

Additional Information

© 1994 National Academy of Sciences. Communicated by Norman Davidson, January 21, 1994 (received for review November 15, 1993). We thank Aram Isaiants for excellent technical assistance and Dirk Krapf of the California Institute of Technology Applied Microsequencing Facility for peptide sequences. This work was supported by grants from the National Institutes of Health (National Institute of Neurological Disorders and Stroke, 28710 and 17660) and National Science Foundation (FAW, GER-9023446) to M.B.K. and fellowships from National Institutes of Health (General Medical Sciences 07616) to M.L.A. and from the Del Webb Foundation to I.S.M. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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August 22, 2023
August 22, 2023