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Norbin is an endogenous regulator of metabotropic glutamate receptor 5 signaling.

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.

SUBMITTER: Wang H

PROVIDER: S-EPMC2796550 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Norbin is an endogenous regulator of metabotropic glutamate receptor 5 signaling.

Wang Hong H Westin Linda L Nong Yi Y Birnbaum Shari S Bendor Jacob J Brismar Hjalmar H Nestler Eric E Aperia Anita A Flajolet Marc M Greengard Paul P

Science (New York, N.Y.) 20091201 5959

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 chan ...[more]

PMID: 20007903

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