Jaffrey S R, Snowman A M, Eliasson M J, Cohen N A, Snyder S H
The Johns Hopkins University School of Medicine, Department of Neuroscience, Pharmacology and Molecular Sciences, Baltimore, Maryland 21205, USA.
Neuron. 1998 Jan;20(1):115-24. doi: 10.1016/s0896-6273(00)80439-0.
Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is important for N-methyl-D-aspartate (NMDA) receptor-dependent neurotransmitter release, neurotoxicity, and cyclic GMP elevations. The coupling of NMDA receptor-mediated calcium influx and nNOS activation is postulated to be due to a physical coupling of the receptor and the enzyme by an intermediary adaptor protein, PSD95, through a unique PDZ-PDZ domain interaction between PSD95 and nNOS. Here, we report the identification of a novel nNOS-associated protein, CAPON, which is highly enriched in brain and has numerous colocalizations with nNOS. CAPON interacts with the nNOS PDZ domain through its C terminus. CAPON competes with PSD95 for interaction with nNOS, and overexpression of CAPON results in a loss of PSD95/nNOS complexes in transfected cells. CAPON may influence nNOS by regulating its ability to associate with PSD95/NMDA receptor complexes.
神经元型一氧化氮合酶（nNOS）产生的一氧化氮（NO）对于N-甲基-D-天冬氨酸（NMDA）受体依赖性神经递质释放、神经毒性及环磷酸鸟苷（cGMP）升高具有重要意义。NMDA受体介导的钙内流与nNOS激活之间的偶联被认为是由于受体与该酶通过中介衔接蛋白PSD95发生物理偶联，这一过程通过PSD95与nNOS之间独特的PDZ-PDZ结构域相互作用实现。在此，我们报告了一种新型nNOS相关蛋白CAPON的鉴定，该蛋白在脑中高度富集且与nNOS有大量共定位。CAPON通过其C末端与nNOS的PDZ结构域相互作用。CAPON与PSD95竞争与nNOS的相互作用，并且CAPON的过表达导致转染细胞中PSD95/nNOS复合物缺失。CAPON可能通过调节nNOS与PSD95/NMDA受体复合物结合的能力来影响nNOS。
