Chapter 2 - Neural Cell Adhesion Molecules in Normal and Abnormal Neural Development

Abstract

The cell–cell and cell–matrix interactions mediated by the adhesion molecules on the cell surface are vital to neural development and plasticity. The neural cell adhesion molecule (NCAM), a member of the immunoglobulin superfamily, promotes cell-to-cell adhesion in the nervous system through a homophilic, Ca2+-independent binding mechanism. NCAM-mediated cell adhesion is involved in the regulation of neural cell migration, neurite outgrowth and fasciculation, and synaptic formation. Polysialic acid (PSA), found as a component of neural tissue, is a linear homopolymer containing sialic acid residues in -2,8-linkage. Polysialylation of the NCAM decreases the homophilic binding of NCAM thereby attenuating cell adhesion. The attachment of PSA to NCAM gives rise to additional mechanisms in modulating cell adhesion. The polysialylation of NCAM is modulated in the developmental stage and is site-specific during the development. Endoneuraminidase N, which specifically cleaves PSA without compromising the cell viability, has been utilized to explore the modulatory effects of PSA upon cell migration. PAS on the NCAM contributes to the motility of migratory cells. The expression levels of NCAM and polysialylated NCAM are critical for neural plasticity, which is dependent on either cell migration and sprouting or the synaptic activity.