神经型一氧化氮合酶的活性调控

一氧化氮是重要的信使分子,在生物体内参与众多生理及病理过程。生物体内存在着复杂的一氧化氮合酶活性调控机制以精确调控一氧化氮的生成。在神经系统中,一氧化氮主要由神经型一氧化氮合酶催化生成。神经型一氧化氮合酶的活性主要受到翻译后水平上钙离子和钙调蛋白的调控,其调控方式包括二聚化、多位点的磷酸化和去磷酸化,以及主要由PDZ结构域介导的蛋白质-蛋白质相互作用。一氧化氮本身对其合酶的活性具有负反馈调控作用。近年来的研究提示,细胞质膜上的脂筏微区在神经性一氧化氮合酶的活性调控中也起到重要的调节作用。

The Regulation of Neuronal Nitric Oxide Synthase Activity

Nitric oxide is an important messenger molecule involved in many vital physiological and pathological processes.In central nervous system,the predominant source of nitric oxide is constituted by neuronal nitric oxide synthase.The activity of neuronal nitric oxide synthase is under the regulation of variety mechanisms to tightly control the production of nitric oxide.Its activity is mainly regulated by calcium/calmodulin at posttranslational level.Other mechanisms including protein dimerization,phosphorylation and dephosphorylation at multiple sites and protein-protein interaction mediated mainly by its N-terminus PDZ domain,the well-studied interacted protein including NMDA receptor,PSD95,CAPON,plasma membrane Ca 2+-ATPase,etc.The generated nitric oxide also has negative feedback regulating effect on the activity of its synthase.In addition,the studies in recent years also implied that the lipid raft microdomain of the plasma membrane may play an important role in the regulation of the activity of neuronal nitric oxide synthase.