ANKYRIN-BINDING ACTIVITY OF NERVOUS-SYSTEM CELL-ADHESION MOLECULES EXPRESSED IN ADULT BRAIN

A family of ankyrin-binding glycoproteins have been identified in adul t rat brain that include alternatively spliced products of the same pr e-mRNA. A composite sequence of ankyrin-binding glycoprotein (ABGP) sh ares 72% amino acid sequence identity with chicken neurofascin, a memb rane-spanning neural cell adhesion molecule in the Ig super-family exp ressed in embryonic brain. ABGP polypeptides and ankyrin associate as pure proteins in a 1:1 molar stoichiometry at a site located in the pr edicted cytoplasmic domain. ABGP polypeptides are expressed late in po stnatal development to approximately the same levels as ankyrin, and c omprise a significant fraction of brain membrane proteins. Immunofluor escence studies have shown that ABGP polypeptides are co-localized wit h ankyrin(B)eta. Major differences in developmental expression have be en reported for neurofascin in embryos compared with the late postnata l expression of ABGP, suggesting that ABGP and neurofascin represent p roducts of gene duplication events that have subsequently evolved in p arallel with distinct roles. Predicted cytoplasmic domains of rat ABGP and chicken neurofascin are nearly identical to each other and closel y related to a group of nervous system cell adhesion molecules with va riable extracellular domains, including L1, Nr-CAM and Ng-CAM of verte brates, and neuroglian of Drosophila. A hypothesis to be evaluated is that ankyrin-binding activity is shared by all of these proteins.