Selective inhibition of polysialyltransferase ST8SiaII by unnatural sialic acids.
Polysialic acid (polySia) is a unique and highly regulated posttranslational modification of the neural cell adhesion molecule (NCAM). The presence of polySia affects NCAM-dependent cell adhesion and plays an important role during brain development, neural regeneration and plastic processes including learning and memory. Polysialylated NCAM is expressed on several neuroendocrine tumors of high malignancy and correlates with poor prognosis. Two closely related enzymes, the polysialyltransferases ST8SiaII and ST8SiaIV, catalyze the biosynthesis of polySia. However, the impact of each enzyme in NCAM polysialylation is not understood. Here, we describe the selective cell-based in vitro inhibition of ST8SiaII using synthetic sialic acid precursors. We provide evidence for different substrate affinities of ST8SiaII and ST8SiaIV. These data open the possibility to study the individual role of the two enzymes during various aspects of brain development and function and in tumorigenesis.
Horstkorte
Rüdiger
R
Institut für Molekularbiologie und Biochemie, Charité-Universitätsmedizin Berlin, D-14195 Berlin-Dahlem, Germany. ruediger.horstkorte@charite.de
Mühlenhoff
Martina
M
Reutter
Werner
W
Nöhring
Sabine
S
Zimmermann-Kordmann
Martin
M
Gerardy-Schahn
Rita
R
D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D020134:Catalytic Domain / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D018922:HL-60 Cells; D006595:Hexosamines / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009438:Neuraminic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012799:Sialyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013379:Substrate Specificity
D006595:Hexosamines; D019006:Neural Cell Adhesion Molecules; D009438:Neuraminic Acids; C008322:mannosamine; C046778:CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid