唾液酸化对小鼠的早期发育至关重要。
Sialylation is essential for early development in mice.
作者信息
Schwarzkopf Martina, Knobeloch Klaus-Peter, Rohde Elvira, Hinderlich Stephan, Wiechens Nicola, Lucka Lothar, Horak Ivan, Reutter Werner, Horstkorte Rüdiger
机构信息
Institut für Molekularbiologie und Biochemie, Fachbereich Humanmedizin, Freie Universität Berlin, Arnimallee 22, D-14195 Berlin-Dahlem, Germany.
出版信息
Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5267-70. doi: 10.1073/pnas.072066199. Epub 2002 Apr 2.
Abstract
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-acetylmannosamine 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.
摘要
唾液酸作为真核细胞糖缀合物上的末端碳水化合物广泛表达。唾液酸化对于多种细胞功能至关重要，如细胞黏附或信号识别，并调节糖蛋白的生物稳定性。唾液酸生物合成的关键酶是双功能UDP-N-乙酰葡糖胺-2-表异构酶/N-乙酰甘露糖胺激酶（UDP-GlcNAc 2-表异构酶），它在细胞质中催化唾液酸生物合成的前两个步骤。我们报道，通过基因靶向使UDP-GlcNAc 2-表异构酶失活会导致小鼠早期胚胎致死，从而强调了这种双功能酶和唾液酸化在发育过程中的基本作用。胚胎干细胞中神经细胞黏附分子的多唾液酸化例证了UDP-GlcNAc 2-表异构酶对特定唾液酸化过程的需求。
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本文引用的文献
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The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy.UDP-N-乙酰葡糖胺2-表异构酶/N-乙酰甘露糖胺激酶基因在隐性遗传性包涵体肌病中发生突变。
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Mice expressing only monosialoganglioside GM3 exhibit lethal audiogenic seizures.仅表达单唾液酸神经节苷脂GM3的小鼠表现出致命的听源性癫痫发作。
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Protein kinase C phosphorylates and regulates UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase.蛋白激酶C使UDP-N-乙酰葡糖胺-2-差向异构酶/N-乙酰甘露糖胺激酶磷酸化并对其进行调节。
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Primary structure and expression analysis of human UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, the bifunctional enzyme in neuraminic acid biosynthesis.人UDP-N-乙酰葡糖胺-2-差向异构酶/N-乙酰甘露糖胺激酶（神经氨酸生物合成中的双功能酶）的一级结构及表达分析
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UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation.UDP-N-乙酰葡糖胺2-差向异构酶：细胞表面唾液酸化的调节因子。
Science. 1999 May 21;284(5418):1372-6. doi: 10.1126/science.284.5418.1372.
9
Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme.人类UDP-N-乙酰葡糖胺2-表异构酶基因突变可导致唾液酸尿症并确定该酶的变构位点。
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Cutting edge: an inducible sialidase regulates the hyaluronic acid binding ability of CD44-bearing human monocytes.前沿：一种可诱导的唾液酸酶调节携带CD44的人单核细胞的透明质酸结合能力。
J Immunol. 1999 May 1;162(9):5058-61.
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