Norbin is an endogenous regulator of metabotropic glutamate receptor 5 signaling.
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.
Wang
Hong
H
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10065, USA.
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
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
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