Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10065, USA.
Science. 2009 Dec 11;326(5959):1554-7. doi: 10.1126/science.1178496.
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.
代谢型谷氨酸受体 5（mGluR5）在哺乳动物中枢神经系统（CNS）中高度表达。它参与多种生理功能，是治疗包括精神分裂症在内的各种 CNS 疾病的靶点。我们报告称，神经元特异性蛋白 Norbin 与体内的 mGluR5 发生物理相互作用，增加了受体的细胞表面定位，并正向调节 mGluR5 信号转导。Norbin 的基因缺失可减弱作为海马突触传递长时程抑制或长时程增强的突触功能的稳定变化，这可作为 mGluR5 依赖性变化的指标。与 mGluR5 基因敲除小鼠或用 mGluR5 选择性拮抗剂处理的小鼠一样，Norbin 基因敲除小鼠表现出一种与精神分裂症啮齿动物模型相关的行为表型，其特征是感觉运动门控和致幻剂诱导的运动活动均发生改变。
