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Science. 2009 Dec 11;326(5959):1554-7. doi: 10.1126/science.1178496.

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

Author information

  • 1Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10065, USA.

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.

KEYWORDS:

LTD; LTP; NMDA; Norbin; calcium oscillation; mGluR5; neurochondrin; schizophrenia

PMID:
20007903
[PubMed - indexed for MEDLINE]
PMCID:
PMC2796550
Free PMC Article

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