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The intracellular concentration of sialic acid regulates the polysialylation of the neural cell adhesion molecule
Author(s) -
Bork Kaya,
Reutter Werner,
Gerardy-Schahn Rita,
Horstkorte Rüdiger
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.08.013
Subject(s) - polysialic acid , sialic acid , neural cell adhesion molecule , glycoconjugate , biochemistry , chemistry , n acetylneuraminic acid , sialidase , cell , enzyme , cell adhesion , microbiology and biotechnology , biology , neuraminidase
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.