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The S-100: A protein family in search of a function

1995; Elsevier BV; Volume: 46; Issue: 1 Linguagem: Inglês

10.1016/0301-0082(94)00062-m

1873-5118

Giorgio Fanò, Silvia Biocca, Stefania Fulle, Maria A. Mariggiò, Silvia Belia, Pietro Calissano,

Medicinal Plants and Neuroprotection

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 (α, β). In the nervous system, the S-100 exists as a mixture composed of ββ and αβ dimers with the monomer β 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 (K d = 0.2 μ m; B max = 4.5 n m), is able to modify the activity of adenylate cyclase, probably via G-proteins. In addition, the Ca 2+ homeostasis is also modulated by S-100 via an increase of specific membrane conductance and/or Ca 2+ release from intracellular stores. "In vitro" and "in vivo" experiments showed that lower (n m) concentrations of extracellular S-100β 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.