The intracellular concentration of sialic acid regulates the polysialylation of the neural cell adhesion molecule.
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.
Bork
Kaya
K
Institut für Biochemie und Molekularbiologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, 14195 Berlin-Dahlem, Germany.
Reutter
Werner
W
Gerardy-Schahn
Rita
R
Horstkorte
Rüdiger
R
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
D009097:Multienzyme Complexes; D019006:Neural Cell Adhesion Molecules; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid