Regulation of cell adhesion by polysialic acid

The polysialylation of neural cell adhesion molecule (NCAM) evolved in vert ebrates to carry out biological functions related to changes in cell positi on and morphology. Many of these effects involve the attenuation of cell in teractions that are not mediated through NCAM's own adhesion properties. A proposed mechanism for this global effect on cell interaction is the steric inhibition of membrane-membrane apposition based solely on polysialic acid (PSA) biophysical properties. However, it remains possible that the intrin sic binding or signaling properties of the NCAM polypeptide are also involv ed. To help resolve this issue, this study uses a quantitative cell detachm ent assay together with cells engineered to display different adhesion rece ptors together with a variety of polysialylated NCAM polypeptide isoforms a nd functional domain deletion mutations. The results obtained indicate that regulation by PSA occurs with adhesion receptors as diverse as an IgCAM, a cadherin and an integrin, and does not require NCAM functional domains oth er than those minimally required for polysialylation. These findings are mo st consistent with the cell apposition mechanism for PSA action, as this mo del predicts that the inhibitory effects of PSA-NCAM on cell adhesion shoul d be independent of the nature of the adhesion system and of any intrinsic binding or signalling properties of the NCAM polypeptide itself.