European Neuroscience Institute at Aberdeen, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom; Division of Molecular Neurobiology, Department of Medical Biochemistry & Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden.
Institute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne NE4 5PL, United Kingdom.
Cell Signal. 2012 Feb;24(2):378-387. doi: 10.1016/j.cellsig.2011.09.028. Epub 2011 Oct 1.
Effective control of the Ca(2+) homeostasis in any living cell is paramount to coordinate some of the most essential physiological processes, including cell division, morphological differentiation, and intercellular communication. Therefore, effective homeostatic mechanisms have evolved to maintain the intracellular Ca(2+) concentration at physiologically adequate levels, as well as to regulate the spatial and temporal dynamics of Ca(2+)signaling at subcellular resolution. Members of the superfamily of EF-hand Ca(2+)-binding proteins are effective to either attenuate intracellular Ca(2+) transients as stochiometric buffers or function as Ca(2+) sensors whose conformational change upon Ca(2+) binding triggers protein-protein interactions, leading to cell state-specific intracellular signaling events. In the central nervous system, some EF-hand Ca(2+)-binding proteins are restricted to specific subtypes of neurons or glia, with their expression under developmental and/or metabolic control. Therefore, Ca(2+)-binding proteins are widely used as molecular markers of cell identity whilst also predicting excitability and neurotransmitter release profiles in response to electrical stimuli. Secretagogin is a novel member of the group of EF-hand Ca(2+)-binding proteins whose expression precedes that of many other Ca(2+)-binding proteins in postmitotic, migratory neurons in the embryonic nervous system. Secretagogin expression persists during neurogenesis in the adult brain, yet becomes confined to regionalized subsets of differentiated neurons in the adult central and peripheral nervous and neuroendocrine systems. Secretagogin may be implicated in the control of neuronal turnover and differentiation, particularly since it is re-expressed in neoplastic brain and endocrine tumors and modulates cell proliferation in vitro. Alternatively, and since secretagogin can bind to SNARE proteins, it might function as a Ca(2+) sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Thus, secretagogin emerges as a functionally multifaceted Ca(2+)-binding protein whose molecular characterization can unravel a new and fundamental dimension of Ca(2+)signaling under physiological and disease conditions in the nervous system and beyond.
有效控制任何活细胞中的钙离子稳态对于协调一些最基本的生理过程至关重要，包括细胞分裂、形态分化和细胞间通讯。因此，已经进化出有效的稳态机制来维持细胞内钙离子浓度在生理上适当的水平，并调节亚细胞分辨率下钙离子信号的时空动力学。EF 手钙离子结合蛋白超家族的成员有效地作为化学计量缓冲剂来减弱细胞内钙离子瞬变，或者作为钙离子传感器，其在钙离子结合时的构象变化触发蛋白-蛋白相互作用，导致细胞状态特异性的细胞内信号事件。在中枢神经系统中，一些 EF 手钙离子结合蛋白仅限于特定亚型的神经元或神经胶质细胞，其表达受发育和/或代谢控制。因此，钙离子结合蛋白被广泛用作细胞身份的分子标志物，同时也预测对电刺激的兴奋性和神经递质释放谱。分泌素是 EF 手钙离子结合蛋白家族的一个新成员，其表达先于胚胎神经系统中许多其他钙离子结合蛋白在后生性、迁移神经元中的表达。分泌素在成年大脑的神经发生过程中持续表达，但局限于成年中枢和周围神经系统和神经内分泌系统中分化神经元的区域化亚群。分泌素可能参与控制神经元的更替和分化，特别是因为它在肿瘤性脑和内分泌肿瘤中重新表达，并在体外调节细胞增殖。或者，由于分泌素可以结合 SNARE 蛋白，它可能作为钙离子传感器/巧合检测器，调节神经递质、神经肽或激素的囊泡胞吐作用。因此，分泌素作为一种功能多样的钙离子结合蛋白出现，其分子特征可以揭示生理和疾病条件下神经系统及其他系统中钙离子信号的新的基本维度。
