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PMID:20007903

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Citation

Wang, H, Westin, L, Nong, Y, Birnbaum, S, Bendor, J, Brismar, H, Nestler, E, Aperia, A, Flajolet, M and Greengard, P (2009) Norbin is an endogenous regulator of metabotropic glutamate receptor 5 signaling. Science 326:1554-7

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.

Links

PubMed PMC2796550 Online version:10.1126/science.1178496

Keywords

Animals; Brain/metabolism; Calcium/metabolism; Calcium Signaling; Cell Line; Cell Membrane/metabolism; Humans; Mice; Mice, Knockout; Motor Activity; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neuronal Plasticity; Protein Binding; Rats; Receptors, Metabotropic Glutamate/genetics; Receptors, Metabotropic Glutamate/metabolism; Schizophrenia/physiopathology; Signal Transduction; Startle Reaction; Synaptic Transmission; Transfection

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:NCDN

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P31424

F

Seeded From UniProt

complete

RAT:GRM5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O35095

F

Seeded From UniProt

complete


See also

References

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