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Science 326 (5959): 1554-1557

Copyright © 2009 by the American Association for the Advancement of Science

Norbin Is an Endogenous Regulator of Metabotropic Glutamate Receptor 5 Signaling

Hong Wang,1 Linda Westin,2 Yi Nong,1 Shari Birnbaum,3 Jacob Bendor,1 Hjalmar Brismar,2,4 Eric Nestler,5 Anita Aperia,2 Marc Flajolet,1,* Paul Greengard1

Abstract: Metabotropic glutamate receptor 5 (mGluR5) is highly expressed in the mammalian central nervous system (CNS). It is involved in multiple physiological functions and is a target for treatment of various CNS disorders, including schizophrenia. We report that Norbin, a neuron-specific protein, physically interacts with mGluR5 in vivo, increases the cell surface localization of the receptor, and positively regulates mGluR5 signaling. Genetic deletion of Norbin attenuates mGluR5-dependent stable changes in synaptic function measured as long-term depression or long-term potentiation of synaptic transmission in the hippocampus. As with mGluR5 knockout mice or mice treated with mGluR5-selective antagonists, Norbin knockout mice showed a behavioral phenotype associated with a rodent model of schizophrenia, as indexed by alterations both in sensorimotor gating and psychotomimetic-induced locomotor activity.

1 Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10065, USA.
2 Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital Q2:09, S-171 76 Stockholm, Sweden.
3 Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
4 Department of Applied Physics, Cell Physics, Royal Institute of Technology, S-106 91 Stockholm, Sweden.
5 Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.

* To whom correspondence should be addressed. E-mail: flajolm{at}rockefeller.edu


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