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Robert J. Wenthold" Trafficking of NMDA receptors"

Abstract :


The NMDA receptor is a critical player in synaptic transmission at glutamatergic synapses.
It is required for many forms of synaptic plasticity, it has been linked to neurite outgrowth and synapse formation, and has been implicated in several neurological and psychiatric disorders. The NMDA receptor is highly concentrated at the postsynaptic membrane of glutamatergic synapses, but it is also found at extrasynaptic sites. Establishing and maintaining the correct number, composition, and location of NMDA receptors is required for synaptic transmission. My research is focused at determining how these receptors are regulated at both the synaptic and extrasynaptic sites. One approach we use is to investigate the role of proteins that interact either directly or indirectly with the receptor. Such proteins may regulate the trafficking of NMDA receptors and control both the number and location of receptors on the cell surface. PDZ proteins, particularly those of the PSD-95 family, interact with NMDA receptors and influence their trafficking. But other proteins, as well, are important in determining the number and location of NMDA receptors.

Selected publications

Grati M, Aggarwal N, Strehler EE, Wenthold RJ. Molecular determinants for differential membrane trafficking of PMCA1 and PMCA2 in mammalian hair cells. J Cell Sci. 2006 Jul 15;119(Pt 14):2995-3007.
Wang CY, Chang K, Petralia RS, Wang YX, Seabold GK, Wenthold RJ. A novel family of adhesion-like molecules that interacts with the NMDA receptor.
J Neurosci. 2006 Feb 22;26(8):2174-83.
Sans N, Wang PY, Du Q, Petralia RS, Wang YX, Nakka S, Blumer JB, Macara IG, Wenthold RJ. mPins modulates PSD-95 and SAP102 trafficking and influences NMDA receptor surface expression. Nat Cell Biol. 2005 Dec;7(12):1179-90. Erratum in: Nat Cell Biol. 2006 Jan;8(1):100.
Prybylowski K, Chang K, Sans N, Kan L, Vicini S, Wenthold RJ. The synaptic localization of NR2B-containing NMDA receptors is controlled by interactions with PDZ proteins and AP-2. Neuron. 2005 Sep 15;47(6):845-57.
Petralia RS, Sans N, Wang YX, Wenthold RJ. Ontogeny of postsynaptic density proteins at glutamatergic synapses. Mol Cell Neurosci. 2005 Jul;29(3):436-52.

Nathalie Sans