Fanò G, Biocca S, Fulle S, Mariggiò M A, Belia S, Calissano P
Instituto di Fisiopatologia Medica, Università G. D'Annunzio, Chieti, Italy.
Prog Neurobiol. 1995 May;46(1):71-82. doi: 10.1016/0301-0082(94)00062-m.
The S-100 is a group of low molecular weight (10-12 kD) calcium-binding proteins highly conserved among vertebrates. It is present in different tissues as dimers of homologous or different subunits (alpha, beta). In the nervous system, the S-100 exists as a mixture composed of beta beta and alpha beta dimers with the monomer beta represented more often. Its intracellular localisation is mainly restricted to the glial cytoplasmic compartment with a small fraction bound to membranes. In this compartment the S-100 acts as a potent inhibitor of phosphorylation on several substrates including the synaptosomal C-Kinase and Tau, a microtubule-associated protein. The S-100 in particular conditions, after binding with specific membrane sites (Kd = 0.2 microM; Bmax = 4.5 nM), is able to modify the activity of adenylate cyclase, probably via G-proteins. In addition, the Ca2+ homeostasis is also modulated by S-100 via an increase of specific membrane conductance and/or Ca2+ release from intracellular stores. "In vitro" and "in vivo" experiments showed that lower (nM) concentrations of extracellular S-100 beta act on glial and neuronal cells as a growth-differentiating factor. On the other hand, higher concentrations of the protein induce apoptosis of some cells such as the sympathetic-like PC12 line. Finally, data obtained from physiological (development, ageing) or pathological (dementia associated with Down's syndrome, Alzheimer's disease) conditions showed that a relationship could be established between the S-100 levels and some aspects of the statii.
S-100是一组低分子量（10 - 12千道尔顿）的钙结合蛋白，在脊椎动物中高度保守。它以同源或不同亚基（α、β）的二聚体形式存在于不同组织中。在神经系统中，S-100以ββ和αβ二聚体的混合物形式存在，其中单体β更为常见。其细胞内定位主要局限于胶质细胞质区室，有一小部分与膜结合。在这个区室中，S-100作为几种底物磷酸化的有效抑制剂，包括突触体C激酶和微管相关蛋白Tau。在特定条件下，S-100与特定膜位点结合后（解离常数Kd = 0.2微摩尔；最大结合量Bmax = 4.5纳摩尔），可能通过G蛋白改变腺苷酸环化酶的活性。此外，S-100还通过增加特定膜电导和/或从细胞内储存释放Ca2+来调节Ca2+稳态。“体外”和“体内”实验表明，较低（纳摩尔）浓度的细胞外S-100β作为生长分化因子作用于胶质细胞和神经元细胞。另一方面，较高浓度的该蛋白会诱导某些细胞凋亡，如交感神经样PC12细胞系。最后，从生理（发育、衰老）或病理（与唐氏综合征、阿尔茨海默病相关的痴呆）条件下获得的数据表明，S-100水平与某些状态方面之间可以建立联系。
