The compartmentalization of cytidine 5′-monophosphate (CMP)-sialic acid synthesis in the cell nucleus (for review Kean 1991; Münster et al. 1998) and its metabolism in the lumen of the Golgi apparatus demonstrates that a system that transports the nucleotide sugar across the Golgi membrane is required. This function is accomplished by the CMP-sialic acid transporter (CST), a highly hydrophobic type III membrane protein (Hirschberg and Snider 1987; Hirschberg et al. 1998). The membrane topology has been identified for murine CST (Eckhardt et al. 1999), but so far no information is available on the tertiary and potential quaternary structure of the protein. The CST provides a key element in the cellular sialylation pathway, and defects in the CST gene lead to drastically reduced levels (Stanley and Siminovitch 1976; Briles et al. 1977) or complete loss (Eckhardt et al. 1996) of sialylated glycoconjugates. The lack of clinical manifestations caused by defects in the CST gene suggests that mutations in this important structure are lethal.


Sialic Acid Golgi Membrane Golgi Vesicle Leukocyte Adhesion Deficiency Cell Surface Glycoconjugates 
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  1. Aoki K, Sun-Wada GH, Segawa H, Yoshioka S, Ishida N, Kawakita M (1999) Expression and activity of chimeric molecules between human UDP-galactose transporter and CMP-sialic acid transporter. J Biochem (Tokyo) 126:940–950CrossRefGoogle Scholar
  2. Berninsone P, Eckhardt M, Gerardy-Schahn R, Hirschberg CB (1997) Functional expression of the murine Golgi CMP-sialic acid transporter in Saccharomyces cerevisiae. J Biol Chem 272:12616–12619PubMedCrossRefGoogle Scholar
  3. Brandan E, Fleischer B (1982) Orientation and role of nucleoside diphosphatase and 5′-nucleotidase in Golgi vesicles from rat liver. Biochemistry 21:4640–4645PubMedCrossRefGoogle Scholar
  4. Briles EB, Li E, Kornfeld S (1977) Isolation of wheat germ agglutinin-resistant clones of Chinese hamster ovary cells deficient in membrane sialic acid and galactose. J Biol Chem 252:1107–1116PubMedGoogle Scholar
  5. Capasso JM, Hirschberg CB (1984) Effect of nucleotides on translocation of sugar nucleotides and adenosine 3′-phosphate 5′-phosphosulfate into Golgi apparatus vesicles. Biochim Biophys Acta 777:133–139PubMedCrossRefGoogle Scholar
  6. Deutscher SL, Nuwayhid N, Stanley P, Briles EI, Hirschberg CB (1984) Translocation across Golgi vesicle membranes: a CHO glycosylation mutant deficient in CMP-sialic acid transport. Cell 39:295–299PubMedCrossRefGoogle Scholar
  7. Eckhardt M, Gerardy-Schahn R (1997) Molecular cloning of the hamster CMP-sialic acid transporter. Eur J Biochem 248:187–192PubMedCrossRefGoogle Scholar
  8. Eckhardt M, Gotza B, Gerardy-Schahn R (1998) Mutants of the CMP-sialic acid transporter causing the Lec2 phenotype. J Biol Chem 273:20189–20195PubMedCrossRefGoogle Scholar
  9. Eckhardt M, Gotza B, Gerardy-Schahn R (1999) Membrane topology of the mammalian CMP-sialic acid transporter. J Biol Chem 274:8779–8787PubMedCrossRefGoogle Scholar
  10. Eckhardt M, Mühlenhoff M, Bethe A, Gerardy-Schahn R (1996) Expression cloning of the Golgi CMP-sialic acid transporter. Proc Natl Acad Sci USA 93:7572–7576PubMedCrossRefGoogle Scholar
  11. Fukuda M (1996) Possible roles of tumor-associated carbohydrate antigens. Cancer Res 56:2237–2244PubMedGoogle Scholar
  12. Harvey BE, Thomas P (1993) Inhibition of CMP-sialic acid transport in human liver and colorectal cancer cell lines by a sialic acid nucleoside conjugate (KI-8110). Biochem Biophys Res Commun 190:571–575PubMedCrossRefGoogle Scholar
  13. Hirschberg CB, Snider MD (1987) Topography of glycosylation in the rough endoplasmic reticulum and Golgi apparatus. Annu Rev Biochem 56:63–87PubMedCrossRefGoogle Scholar
  14. Hirschberg CB, Robbins PW, Abeijon C (1998) Transporters of nucleotide sugars, ATP, and nucleotide sulfate in the endoplasmic reticulum and Golgi apparatus. Annu Rev Biochem 67:49–69PubMedCrossRefGoogle Scholar
  15. Ishida N, Ito M, Yoshioka S, Sun-Wada GH, Kawakita M (1998) Functional expression of human Golgi CMP-sialic acid transporter in the Golgi complex of a transporter-deficient Chinese hamster ovary cell mutant. J Biochem (Tokyo) 124:171–178CrossRefGoogle Scholar
  16. Kean EL (1991) Sialic acid activation. Glycobiology 1:441–447PubMedCrossRefGoogle Scholar
  17. Kelm S, Schauer R (1997) Sialic acids in molecular and cellular interactions. Int Rev Cytol 175:137–240PubMedCrossRefGoogle Scholar
  18. Keppler OT, Peter ME, Hinderlich S, Moldenhauer G, Stehling P, Schmitz I, Schwartz-Albiez R, Reutter W, Pawlita M (1999) Differential sialylation of cell surface glycoconjugates in a human B lymphoma cell line regulates susceptibility for CD95 (APO-1/Fas)-mediated apoptosis and for infection by a lymphotropic virus. Glycobiology 9:557–569PubMedCrossRefGoogle Scholar
  19. Milla ME, Hirschberg CB (1989) Reconstitution of Golgi vesicle CMP-sialic acid and adenosine 3′-phosphate 5′-phosphosulfate transport into proteoliposomes. Proc Natl Acad Sci USA 86:1786–1790PubMedCrossRefGoogle Scholar
  20. Münster AK, Eckhardt M, Potvin B, Mühlenhoff M, Stanley P, Gerardy-Schahn R (1998) Mammalian cytidine 5′-monophosphate N-acetylneuraminic acid synthetase: a nuclear protein with evolutionarily conserved structural motifs. Proc Natl Acad Sci USA 95:9140–9145PubMedCrossRefGoogle Scholar
  21. Perez M, Hirschberg CB (1987) Transport of sugar nucleotides into the lumen of vesicles derived from rat liver rough endoplasmic reticulum and Golig apparatus. Methods Enzymol 138:709–715PubMedCrossRefGoogle Scholar
  22. Stanley P, Siminovitch L (1976) Selection and characterization of Chinese hamster ovary cells resistant to the cytotoxicity of lectins. In Vitro 12:208–215PubMedCrossRefGoogle Scholar
  23. Tiralongo J, Abo S, Danylec B, Gerardy-Schahn R, von Itzstein M (2000) A highthroughput assay for rat liver Golgi and Saccharomyces cerevisiae-expressed murine CMP-N-acetylneuraminic acid transport proteins. Anal Biochem 285:21–32PubMedCrossRefGoogle Scholar

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© Springer Japan 2002

Authors and Affiliations

  • Rita Gerardy-Schahn
    • 1
  1. 1.Institut für Physiologische ChemieProteinstruktur Medizinische Hochschule HannoverHannoverGermany

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