title: The intracellular concentration of sialic acid regulates the polysialylation of the neural cell adhesion molecule.
abstract: Sialic acids are expressed as terminal sugars in many glycoconjugates and play an important role during development and regeneration, as they are involved as polysialic acid in a variety of cell-cell interactions mediated by the neural cell adhesion molecule NCAM. The key enzyme for the biosynthesis of sialic acid is the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine-kinase (GNE). Mutations in the binding site of the feedback inhibitor CMP-sialic acid of the GNE leads to sialuria, a disease in which patients produce sialic acid in gram scale. Here, we report on the consequences after expression of a sialuria-mutated GNE. Expression of the sialuria-mutated GNE leads to a dramatic increase of both cellular sialic acid and polysialic acid on NCAM. This could also be achieved by application of the sialic acid precursor N-acetylmannosamine. Our data suggest that biosynthesis of sialic acid regulates and limits the synthesis of polysialic acid.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, 14195 Berlin-Dahlem, Germany.
authors.forename: Kaya
authors.initials: K
authors.lastname: Bork
authors.forename: Werner
authors.initials: W
authors.lastname: Reutter
authors.forename: Rita
authors.initials: R
authors.lastname: Gerardy-Schahn
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Horstkorte
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000096:biosynthesis* / Q000737:chemistry; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D029461:Sialic Acid Storage Disease / Q000235:genetics / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D019006:Neural Cell Adhesion Molecules; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid