Calcium-dependent interaction between the large myelin-associated glycoprotein and S100 beta

The myelin-associated glycoprotein is a transmembrane cell adhesion molecul e expressed by myelinating glial cells of the nervous system. So far, only protein kinases have been reported to interact with the cytoplasmic domains of the two isoforms of the myelin-associated glycoprotein. We report here the identification of the first nonkinase intracellular ligand for the larg e isoform of the myelin-associated glycoprotein as the S100 beta protein. T he interaction is dependent on the presence of calcium. We have also locali zed the S100 beta-binding site in the cytoplasmic domain specific to the la rge myelin-associated glycoprotein isoform to a putative basic amphipathic alpha-helix. A synthetic peptide corresponding to this region bound to S100 beta in a calcium-dependent manner with a stoichiometric ratio of 1:1 (K-D approximate to 7 mu M) We suggest that the observed interaction may play a role in the regulation of the myelinating glial cell cytoskeleton and the divalent cation-dependent signal transduction events during myelin formatio n and maintenance.