title: 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.
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10065, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Linda
authors.initials: L
authors.lastname: Westin
authors.forename: Yi
authors.initials: Y
authors.lastname: Nong
authors.forename: Shari
authors.initials: S
authors.lastname: Birnbaum
authors.forename: Jacob
authors.initials: J
authors.lastname: Bendor
authors.forename: Hjalmar
authors.initials: H
authors.lastname: Brismar
authors.forename: Eric
authors.initials: E
authors.lastname: Nestler
authors.forename: Anita
authors.initials: A
authors.lastname: Aperia
authors.forename: Marc
authors.initials: M
authors.lastname: Flajolet
authors.forename: Paul
authors.initials: P
authors.lastname: Greengard
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity; D011485:Protein Binding; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D013216:Reflex, Startle; D012559:Schizophrenia / Q000503:physiopathology; D015398:Signal Transduction; D009435:Synaptic Transmission; D014162:Transfection
chemical_list: C578935:GRM5 protein, human; C578936:Grm5 protein, mouse; C578937:Grm5 protein, rat; D009419:Nerve Tissue Proteins; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C422102:SFAP75 protein, mouse; D002118:Calcium