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Norbin Is an Endogenous Regulator of Metabotropic Glutamate Receptor 5 Signaling
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2009 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 326, no 5959, 1554-1557 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 326, no 5959, 1554-1557 p.
Keyword [en]
long-term potentiation, prepulse inhibition, allosteric modulators, neurite-outgrowth, mglur5 antagonist, protein, brain, nmda, mice, phosphorylation
Identifiers
URN: urn:nbn:se:kth:diva-19039DOI: 10.1126/science.1178496ISI: 000272623600062Scopus ID: 2-s2.0-72149125657OAI: oai:DiVA.org:kth-19039DiVA: diva2:337086
Note
QC 20100525Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically approved

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Brismar, Hjalmar

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