神经颗粒素:一种脑特异性蛋白质

Neurogranin:A Brain-specific Protein

神经颗粒素 (Neurogranin ,Ng)是一种新发现的由 78个氨基酸组成的脑特异性蛋白 ,主要分布于人类或动物的大脑皮层、海马和嗅球等脑区的神经突触后。作为Calpacitin蛋白家族中的一员 ,Ng是蛋白激酶C的天然作用底物及钙调蛋白 (CaM )的储库。在生理状态下 ,Ng与CaM结合形成复合体 ,而在蛋白激酶C或氧化剂的作用下 ,Ng可被磷酸化、氧化及谷胱甘肽化等化学修饰 ,降低其与CaM的亲和力 ,从而参与对CaM及CaM 激活的蛋白酶 ,如CaM 依赖性NO合酶、CaM 依赖性蛋白激酶II(CaMKII)及CaM 依赖性腺苷酸环化酶的调节。同时 ,由于CaM 依赖性蛋白酶大多参与长时程增强 (LTP)和长时程抑制 (LTD)的诱导 ,并且Ng的基因表达和蛋白质合成与神经元的突触形成、分化同步 ,因此 ,Ng可能在学习、记忆、神经系统发育 (可塑性 )等生理性变化中具有重要作用。此外 ,一些研究表明 ,Ng还可能参与甲状腺机能减退、睡眠剥夺。

Neurogranin (Ng) is a newly discovered brain specific protein composed of 78 amino acid residues, which mainly located postsynaptically in the cerebral cortex, hippocampus and olfactory bulb in adult human or animals. As a member of calpacitin family, Ng is a protein kinase C (PKC) substrate and calmodulin (CaM) reservoir. In the physiological conditions, Ng forms a complex with CaM, and its CaM binding affinity was modulated by phosphorylation, oxidation and glutathiolation under the activation of PKC or oxidant stress, which may be involved in the regulation of CaM and CaM activated proteins, such as CaM dependent nitric oxide synthase (NOS), CaM dependent protein kinase II (CaMKII) and CaM dependent adenylate cyclase (AC). Since most of CaM activated proteins were involved in long term potentiation (LTP) and long term depression (LTD), and the timing pattern of Ng gene expression and protein synthesis are coincidence with synaptogenesis and development, it is suggested that Ng may play an important role in learning, memory and neuroplasticity. In addition, it was found that the changes of Ng expression might associate with certain cerebral pathophysiologic disorders, such as hypothyroidism, sleep deprivation, brain aging and cerebral hypoxic preconditioning.