Control of NCAM polysialylation by the differential expression of polysialyltransferases ST8SiaII and ST8SiaIV

Abstract

Polysialic acid (PSA) is a developmentally regulated carbohydrate consisting of alpha-2,8-linked sialic acid residues attached to the neural cell adhesion molecule NCAM. PSA promotes plasticity of cell-cell interactions in the 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 synthesize PSA. However, in vivo studies have demonstrated that in the majority of PSA-positive tissues the two polysialyltransferases are expressed simultaneously. Therefore, this study was undertaken to elucidate in which way the individual enzymes contribute to PSA expression under in vivo conditions. Using a semiquantitative RT-PCR strategy PSA-positive human tumor cell lines were screened for expression of ST8SiaII and ST8SiaIV at the mRNA level. Divergent patterns observed in some cell lines suggest that polysialyltransferases are independently regulated at the transcriptional level. In subsequent analyses the different mRNA levels of ST8SiaII and ST8SiaIV in these tumor cells were correlated with the degree of PSA expression and the cellular capacity to rapidly synthesize PSA. Our data indicate that ST8SiaIV is the major regulator of NCAM polysialylation in vivo.