THE S-100 - A PROTEIN FAMILY IN SEARCH OF A FUNCTION

The S-100 is a group of low molecular weight (10-12 kD) calcium-bindin g proteins highly conserved among vertebrates. It is present in differ ent 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 oft en. Its intracellular localisation is mainly restricted to the glial c ytoplasmic compartment with a small fraction bound to membranes. In th is 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, af ter binding with specific membrane sites (K-d = 0.2 mu M; B-max = 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+ relea se 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 th e other hand, higher concentrations of the protein induce apoptosis of some cells such as the sympathetic-like PC12 line. Finally, data obta ined from physiological (development, ageing) or pathological (dementi a associated with Down's syndrome, Alzheimer's disease) conditions sho wed that a relationship could be established between the S-100 levels and some aspects of the statii.