神经钙蛋白δ的功能及其分子作用机制

神经钙蛋白δ(neurocalcinδ)作为神经钙敏感蛋白(neuronal calcium sensors,NCSs)家族的重要成员之一,具有分布广泛、结构较保守的特性.早期研究发现,神经钙蛋白δ具有两对EF手结构(EF1,EF2,EF3和EF4).EF1不能结合Ca2+,而EF2、EF3和EF4与Ca2+结合能促使其N端豆蔻酰暴露,进而实现其由细胞质到细胞质膜的转移定位以及与靶蛋白的结合,从而发挥重要效应.本综述根据神经钙蛋白δ的"Ca2+-豆蔻酰基开关"特性,一方面介绍其能与膜鸟苷酸环化酶反应,参与cGMP信号转导,进而影响视觉和嗅觉,甚至血压等生物学活动;另一方面,介绍神经钙蛋白δ通过与S100β、网格蛋白、肌动蛋白、微管等蛋白质之间的相互作用,并参与细胞内囊泡运输,从而影响细胞内大分子包装、运输等过程.本文还阐明了神经钙蛋白δ参与精子发生、细胞癌变、肾病发生等过程.由于神经钙蛋白δ对了解某些疾病的发生原理、信号转导过程、细胞内信息调控网络等具有重要意义,本综述将为研究相关疾病提供新的研究方向与理论基础.

Functions and Molecular Mechanism of Neurocalcin δ

Neurocalcin δ is an important member of neuronal calcium sensor (NCS) family which is wide-expression and conservative. Neurocalcin δ consists of two pairs of EF-hand calciumbinding loop sequence (EF1, EF2, EF3 and EF4). Previous studies showed that，given the disabled EF1, neurocalcin δ binds Ca²⁺ via its EF2, EF3 and EF4 motifs, therefore exposes a covalently attached myristoyl at the N-terminus, resulting in translocation of neurocalcin δ from cytoplasm to membrane in a Ca ^2+-dependent manner. This review focused on its “Ca ^2+-myristoyl switch” characteristic. On the one hand, the roles of neurocalcin δ were introduced in vision, olfaction and even blood pressure through its reacting with membrane guanylate cyclase, which involved in cGMP signaling pathway. On the other hand, the potential roles of neurocalcin δ in vesicular trafficking, the interaction between neurocalcin δ and its protein patners S100β, actin, clathrin and tubulin were illustrated. Furthermore, neurocalcin δ may be involved in the progresses of spermatogenesis, tumorigenesis and diabetic nephropathy. The exploration of neurocalcin δ shed light on the pathology of some disease, signal transduction and intracellular regulatory network. This review may provide a new research direction or theoretical basis for related disease studies.