Calcium-dependent interaction between the large myelin-associated glycoprotein and S100beta

The myelin-associated glycoprotein is a transmembrane cell adhesion molecule 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 large isoform of the myelin-associated glycoprotein as the S100beta protein. The interaction is dependent on the presence of calcium. We have also localized the S100beta-binding site in the cytoplasmic domain specific to the large myelin-associated glycoprotein isoform to a putative basic amphipathic alpha-helix. A synthetic peptide corresponding to this region bound to S100beta in a calcium-dependent manner with a stoichiometric ratio of 1:1 (K(D) approximately 7 microM). 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 formation and maintenance.