Norbin is an endogenous regulator of metabotropic glutamate receptor 5 signaling

Hong Wang, Linda Westin, Yi Nong, Shari Birnbaum, Jacob Bendor, Hjalmar Brismar, Eric Nestler, Anita Aperia, Marc Flajolet, Paul Greengard

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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.

Original languageEnglish (US)
Pages (from-to)1554-1557
Number of pages4
JournalScience
Volume326
Issue number5959
DOIs
StatePublished - Dec 11 2009

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    Wang, H., Westin, L., Nong, Y., Birnbaum, S., Bendor, J., Brismar, H., Nestler, E., Aperia, A., Flajolet, M., & Greengard, P. (2009). Norbin is an endogenous regulator of metabotropic glutamate receptor 5 signaling. Science, 326(5959), 1554-1557. https://doi.org/10.1126/science.1178496