MOLECULAR CHARACTERIZATION OF EUKARYOTIC POLYSIALYLTRANSFERASE-1

POLYSIALIC acid (PSA) is a dynamically regulated product of posttransl ational modification of the neural cell adhesion molecule, NCAM(1,2). Presence of the large anionic carbohydrate modulates NCAM binding prop erties and, by increasing the intercellular space, influences interact ions between other cell surface molecules(1-5). PSA expression underli es cell type- and developmental-specific alterations(6) and correlates with stages of cellular motility(6-8), In the adult, PSA becomes rest ricted to regions of permanent neural plasticity and regenerating neur al and muscle tissues(6,9,10). Recent data implicate its important fun ction in spatial learning and memory(11,12), and in tumour biology(13- 16). Here we describe the molecular characterization of polysialyltran sferase-1, the key enzyme of eukaryotic PSA synthesis. In reconstituti on experiments, the newly cloned enzyme induces PSA synthesis in all N CAM-expressing cell lines. Our data therefore represent convincing evi dence that the polycondensation of alpha-2,8-linked sialic acids in ma mmals is the result of a single enzymatic activity and provide a new b asis for studying the functional role of PSA in neuro- and tumour biol ogy.