Phosphorylation of serine 774 of the neural cell adhesion molecule (NCAM) is involved in the interaction with collapsin response mediator protein-2

Abstract

The neural cell adhesion molecule NCAM is a major adhesion receptor involved in the development and regeneration of the nervous system. It is expressed in three major isoforms of which two have large intracellular domains of different lengths (NCAM140 and NCAM180). Several intracellular ligands of NCAM have been described. One of them is the collapsin response mediator protein-2 (CRMP-2), which is known to be involved in cell differentiation and axonal growth. The cytoplasmic domains of NCAM contain up to 49 phosphorylation sites and it has been demonstrated recently that the phosphorylation of serine 774 is crucial for NCAM-mediated signal transduction and neurite outgrowth. Here we analyzed the interaction of NCAM with CRMP-2 in more detail using a biochemical approach. We found that CRMP-2 binds specifically to NCAM180 in a sequence between amino acid 788 and 819. In addition we could demonstrate that serine 774, which has been shown previously to be phosphorylated and involved in neurite outgrowth, is also important for the interaction of CRMP-2 with NCAM.