The intracellular concentration of sialic acid regulates the polysialylation of the neural cell adhesion molecule

• Published in: FEBS letters Vol. 579; no. 22; pp. 5079 - 5083
• Main Authors: Bork, Kaya, Reutter, Werner, Gerardy-Schahn, Rita, Horstkorte, Rüdiger
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 12.09.2005
• Subjects: Animals; CHO Cells; Cricetinae; Humans; Multienzyme Complexes - genetics; Multienzyme Complexes - metabolism; N-Acetylmannosamine; N-Acetylneuraminic Acid - biosynthesis; N-Acetylneuraminic Acid - chemistry; Neural Cell Adhesion Molecules - chemistry; Neural Cell Adhesion Molecules - metabolism; Sialic Acid Storage Disease - genetics; Sialic Acid Storage Disease - metabolism; Sialyltransferases - genetics; Sialyltransferases - metabolism; UDP- N-Acetylglucosamine 2-epimerase/ N-acetylmannosaminekinase; N-Acetylmannosamine; UDP- N-Acetylglucosamine 2-epimerase/ N-acetylmannosaminekinase
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2005.08.013

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.