Sialylation is essential for early development in mice

被引:288
作者
Schwarzkopf, M
Knobeloch, KP
Rohde, E
Hinderlich, S
Wiechens, N
Lucka, L
Horak, I
Reutter, W
Horstkorte, R
机构
[1] Free Univ Berlin, Fachbereich Humanmed, Inst Mol Biol & Biochem, D-14195 Berlin, Germany
[2] Free Univ Berlin, Forsch Inst Mol Pharmakol, D-12207 Berlin, Germany
关键词
D O I
10.1073/pnas.072066199
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Sialic acids are widely expressed as terminal carbohydrates on glycoconjugates of eukaryotic cells. Sialylation is crucial for a variety of cellular functions, such as cell adhesion or signal recognition, and regulates the biological stability of glycoproteins. The key enzyme of sialic acid biosynthesis is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetyImannosamine kinase (UDP-GlcNAc 2-epimerase), which catalyzes the first two steps of sialic acid biosynthesis in the cytosol. We report that inactivation of the UDP-GlcNAc 2-epimerase by gene targeting causes early embryonic lethality in mice, thereby emphasizing the fundamental role of this bifunctional enzyme and sialylation during development. The need of UDP-GlcNAc 2-epimerase for a defined sialylation process is exemplified with the polysialylation of the neural cell adhesion molecule in embryonic stem cells.
引用
收藏
页码:5267 / 5270
页数:4
相关论文
共 30 条
[1]  
[Anonymous], 1994, MANIPULATING MOUSE E
[2]   Sialylation of the sialic acid binding lectin sialoadhesin regulates its ability to mediate cell adhesion [J].
Barnes, YC ;
Skelton, TP ;
Stamenkovic, I ;
Sgroi, DC .
BLOOD, 1999, 93 (04) :1245-1252
[3]   INACTIVATION OF THE N-CAM GENE IN MICE RESULTS IN SIZE-REDUCTION OF THE OLFACTORY-BULB AND DEFICITS IN SPATIAL-LEARNING [J].
CREMER, H ;
LANGE, R ;
CHRISTOPH, A ;
PLOMANN, M ;
VOPPER, G ;
ROES, J ;
BROWN, R ;
BALDWIN, S ;
KRAEMER, P ;
SCHEFF, S ;
BARTHELS, D ;
RAJEWSKY, K ;
WILLE, W .
NATURE, 1994, 367 (6462) :455-459
[4]   The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy [J].
Eisenberg, I ;
Avidan, N ;
Potikha, T ;
Hochner, H ;
Chen, M ;
Olender, T ;
Barash, M ;
Shemesh, M ;
Sadeh, M ;
Grabov-Nardini, G ;
Shmilevich, I ;
Friedmann, A ;
Karpati, G ;
Bradley, WG ;
Baumbach, L ;
Lancet, D ;
Ben Asher, E ;
Beckmann, JS ;
Argov, Z ;
Mitrani-Rosenbaum, S .
NATURE GENETICS, 2001, 29 (01) :83-87
[5]   ESTABLISHMENT IN CULTURE OF PLURIPOTENTIAL CELLS FROM MOUSE EMBRYOS [J].
EVANS, MJ ;
KAUFMAN, MH .
NATURE, 1981, 292 (5819) :154-156
[6]   OCCURRENCE OF ALPHA-2-8 LINKED POLYSIALOSYL UNITS IN A NEURAL CELL-ADHESION MOLECULE [J].
FINNE, J ;
FINNE, U ;
DEAGOSTINIBAZIN, H ;
GORIDIS, C .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1983, 112 (02) :482-487
[7]   A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver - Purification and characterization of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase [J].
Hinderlich, S ;
Stasche, R ;
Zeitler, R ;
Reutter, W .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (39) :24313-24318
[8]   Biosynthesis of N-acetylneuraminic acid in cells lacking UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase [J].
Hinderlich, S ;
Berger, M ;
Keppler, OT ;
Pawlita, M ;
Reutter, W .
BIOLOGICAL CHEMISTRY, 2001, 382 (02) :291-297
[9]   Protein kinase C phosphorylates and regulates UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase [J].
Horstkorte, R ;
Nöhring, S ;
Danker, K ;
Effertz, K ;
Reutter, W ;
Lucka, L .
FEBS LETTERS, 2000, 470 (03) :315-318
[10]   Tissue expression and amino acid sequence of murine UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase [J].
Horstkorte, R ;
Nöhring, S ;
Wiechens, N ;
Schwarzkopf, M ;
Danker, K ;
Reutter, W ;
Lucka, L .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1999, 260 (03) :923-927