Document Detail

The intracellular concentration of sialic acid regulates the polysialylation of the neural cell adhesion molecule.
MedLine Citation:
PMID:  16137682     Owner:  NLM     Status:  MEDLINE    
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.
Kaya Bork; Werner Reutter; Rita Gerardy-Schahn; Rüdiger Horstkorte
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  FEBS letters     Volume:  579     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-06     Completed Date:  2005-10-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  5079-83     Citation Subset:  IM    
Institut für Biochemie und Molekularbiologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, 14195 Berlin-Dahlem, Germany.
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MeSH Terms
CHO Cells
Multienzyme Complexes / genetics,  metabolism*
N-Acetylneuraminic Acid / biosynthesis*,  chemistry
Neural Cell Adhesion Molecules / chemistry*,  metabolism
Sialic Acid Storage Disease / genetics,  metabolism
Sialyltransferases / genetics,  metabolism
Reg. No./Substance:
0/Multienzyme Complexes; 0/Neural Cell Adhesion Molecules; 0/UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase; 131-48-6/N-Acetylneuraminic Acid; EC 2.4.99.-/Sialyltransferases

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