Control of NCAM polysialylation by the differential expression of polysialyltransferases ST8Siall and ST8SialV

Polysialic acid (PSA) is a developmentally regulated carbohydrate consistin g of alpha -2,8-linked sialic acid residues attached to the neural cell adh esion molecule NCAM. PSA promotes plasticity of cell-cell interactions in t he nervous system and appears linked to the malignant potential of several tumors. Two enzymes, the polysialyltransferases ST8SiaII (STX) and ST8SiaIV (PST) have been identified and shown to be independently able to synthesiz e PSA. However, in vivo studies have demonstrated that in the majority of P SA-positive tissues the two polysialyltransferases are expressed simultaneo usly. Therefore, this study was undertaken to elucidate in which way the in dividual enzymes contribute to PSA expression under in vivo conditions. Usi ng a semiquantitative RT-PCR strategy PSA-positive human tumor cell lines w ere screened for expression of ST8SiaII and ST8SiaIV at the mRNA level. Div ergent patterns observed in some cell lines suggest that polysialyltransfer ases are independently regulated at the transcriptional level. In subsequen t analyses the different mRNA levels of ST8SiaII and STgSiaIV in these tumo r cells were correlated with the degree of PSA expression and the cellular capacity to rapidly synthesize PSA. Our data indicate that STgSiaIV is the major regulator of NCAM polysialylation in vivo.