Extracellular Protein Interactions Mediated by the Neural Cell Adhesion Molecule, NCAM: Heterophilic Interactions Between NCAM and Cell Adhesion Molecules, Extracellular Matrix Proteins, and Viruses

Abstract

Cell adhesion molecules (CAMs) mediate cell-to-cell interactions and interactions between cells and the extracellular matrix (ECM). The neural cell adhesion molecule (NCAM), a prototypic member of the immunoglobulin (Ig) superfamily of CAMs, mediates adhesion through homophilic and heterophilic interactions, thereby modulating a range of biological processes. This review summarizes interactions between NCAM and other CAMs and ECM proteins. Additionally, the role of NCAM as a receptor for rabies virus, and its implications in rabies infections is briefly described. Interactions between NCAM and its heterophilic partners involve most of the NCAM extracellular modules and are mediated via amino acids and carbohydrates. The interactions promote cell adhesion and trigger signal transduction and alterations in cytoskeletal dynamics and organization. Heterophilic NCAM interactions may modulate, or be modulated by, homophilic NCAM interactions. Furthermore, some of the interactions are mutually exclusive, whereas others might lead to the formation of multimeric protein complexes. Consequently, biological processes affected by NCAM interactions are regulated in a complex manner involving many extracellular protein interactions.