Molecular characterization of eukaryotic polysialyltransferase-1

Polysialic acid (PSA) is a dynamically regulated product of post-translational modification of the neural cell adhesion molecule, NCAM [1,2]. Presence of the large anionic carbohydrate modulates NCAM binding properties and, by increasing the intercellular space, influences interactions between other cell surface molecules [1-5]. PSA expression underlies cell type- and developmental-specific alterations [6] and correlates with stages of cellular motility [6-8]. In the adult, PSA becomes restricted to regions of permanent neural plasticity and regenerating neural and muscle tissues [6,9,10]. Recent data implicate its important function in spatial learning and memory [11,12], and in tumour biology [13-16]. Here we describe the molecular characterization of polysialytransferase-1, the key enzyme of eukaryotic PSA synthesis. In reconstitution experiments, the newly cloned enzyme induces PSA synthesis in all NCAM-expressing cell lines. Our data therefore represent convincing evidence that the polycondensation of alpha-2,8-linked sialic acids in mammals is the result of a single enzymatic activity and provide a new basis for studying the functional role of PSA in neuro- and tumour biology.