Molecular characterization of eukaryotic polysialyltransferase-1

Abstract

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 alterations⁶ 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 polysialyltransferase-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 α–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.