Abstract
GDP-fucose is used by fucosyltransferases in both the Golgi and endoplasmic reticulum (ER). As it is synthesized in the cytoplasm, transport into the lumen of the secretory pathway organelles is required. The first indication that GDP-fucose, like other nucleotide sugars, is transported by a carrier-mediated process was obtained by Sommers and Hirschberg (1982). The gene encoding the GDP-fucose transporter was identified independently by two groups using complementation cloning in patient-derived cells (Lübke et al. 2001; Lühn et al. 2001). These patients were suffering from leukocyte adhesion deficiency II (LAD II), also known as congenital disorder of glycosylation (CDG) type IIc. LAD II patients were originally described as having a deficiency of the fucosylated glycan Sialyl-Lewis X (Etzioni et al. 1992; Etzioni 1994; Phillips et al. 1995). The lack of fucose likely prevents interaction of the endothelial adhesion molecules E- and P-selectin with glycoproteins present on leukocytes. The latter are then unable to migrate through the endothelial layer to reach the sites of inflammation (Wild et al. 2002). In addition to the immunological problems, LAD II patients present characteristic symptoms of CDG patients such as severe mental and growth retardation (Etzioni 2010).
Keywords
- Nucleotide Sugar
- SLC35 Family
- Leukocyte Adhesion Deficiency
- Aleuria Aurantia Lectin
- Complementation Cloning
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, access via your institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Becker DJ, Lowe JB (1999) Leukocyte adhesion deficiency type II. Biochim Biophys Acta 1455:193–204
Chen W, Tang J, Stanley P (2005) Suppressors of alpha(1,3)fucosylation identified by expression cloning in the LEC11B gain-of-function CHO mutant. Glycobiology 15:259–269
Dean N, Zhang YB, Poster JB (1997) The VRG4 gene is required for GDP-mannose transport into the lumen of the Golgi in the yeast, Saccharomyces cerevisiae. J Biol Chem 272:31908–31914
Eckhardt M, Gotza B, Gerardy-Schahn R (1999) Membrane topology of the mammalian CMP-sialic acid transporter. J Biol Chem 274:8779–8787
Engel J, Schmalhorst PS, Routier FH (2012) Biosynthesis of the fungal cell wall polysaccharide galactomannan requires intraluminal GDP-mannose. J Biol Chem 287:44418–44424
Etzioni A (1994) Adhesion molecule deficiencies and their clinical significance. Cell Adhes Commun 2:257–260
Etzioni A (2010) Defects in the leukocyte adhesion cascade. Clin Rev Allergy Immunol 38:54–60
Etzioni A, Frydman M, Pollack S, Avidor I, Phillips ML, Paulson JC, Gershoni-Baruch R (1992) Brief report: recurrent severe infections caused by a novel leukocyte adhesion deficiency. N Engl J Med 327:1789–1792
Foxall C, Watson SR, Dowbenko D, Fennie C, Lasky LA, Kiso M, Hasegawa A, Asa D, Brandley BK (1992) The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewis(x) oligosaccharide. J Cell Biol 117:895–902
Geisler C, Kotu V, Sharrow M, Rendic D, Poltl G, Tiemeyer M, Wilson IB, Jarvis DL (2012) The Drosophila neurally altered carbohydrate mutant has a defective Golgi GDP-fucose transporter. J Biol Chem 287:29599–29609
Hanna S, Etzioni A (2012) Leukocyte adhesion deficiencies. Ann N Y Acad Sci 1250:50–55
Haryadi R, Zhang P, Chan KF, Song Z (2013) CHO-gmt5, a novel CHO glycosylation mutant for producing afucosylated and asialylated recombinant antibodies. Bioengineered 4:90–94
Hellbusch CC, Sperandio M, Frommhold D, Yakubenia S, Wild MK, Popovici D, Vestweber D, Gröne HJ, von Figura K, Lübke T, Körner C (2007) Golgi GDP-fucose transporter-deficient mice mimic congenital disorder of glycosylation IIc/leukocyte adhesion deficiency II. J Biol Chem 282:10762–10772
Helmus Y, Denecke J, Yakubenia S, Robinson P, Lühn K, Watson DL, McGrogan PJ, Vestweber D, Marquardt T, Wild MK (2006) Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter. Blood 107:3959–3966
Hidalgo A, Ma S, Peired AJ, Weiss LA, Cunningham-Rundles C, Frenette PS (2003) Insights into leukocyte adhesion deficiency type 2 from a novel mutation in the GDP-fucose transporter gene. Blood 101:1705–1712
Hong K, Ma D, Beverley SM, Turco SJ (2000) The Leishmania GDP-mannose transporter is an autonomous, multi-specific, hexameric complex of LPG2 subunits. Biochemistry 39:2013–2022
Ishida N, Kawakita M (2004) Molecular physiology and pathology of the nucleotide sugar transporter family (SLC35). Pflugers Arch 447:768–775
Ishikawa HO, Ayukawa T, Nakayama M, Higashi S, Kamiyama S, Nishihara S, Aoki K, Ishida N, Sanai Y, Matsuno K (2010) Two pathways for importing GDP-fucose into the endoplasmic reticulum lumen function redundantly in the O-fucosylation of Notch in Drosophila. J Biol Chem 285:4122–4129
Ishikawa HO, Higashi S, Ayukawa T, Sasamura T, Kitagawa M, Harigaya K, Aoki K, Ishida N, Sanai Y, Matsuno K (2005) Notch deficiency implicated in the pathogenesis of congenital disorder of glycosylation IIc. Proc Natl Acad Sci USA 102:18532–18537
Karsan A, Cornejo CJ, Winn RK, Schwartz BR, Way W, Lannir N, Gershoni-Baruch R, Etzioni A, Ochs HD, Harlan JM (1998) Leukocyte adhesion deficiency type II is a generalized defect of de novo GDP-fucose biosynthesis. Endothelial cell fucosylation is not required for neutrophil rolling on human nonlymphoid endothelium. J Clin Invest 101:2438–2445
Körner C, Linnebank M, Koch HG, Harms E, von Figura K, Marquardt T (1999) Decreased availability of GDP-L-fucose in a patient with LAD II with normal GDP-D-mannose dehydratase and FX protein activities. J Leukoc Biol 66:95–98
Le Gall S, Neuhof A, Rapoport T (2004) The endoplasmic reticulum membrane is permeable to small molecules. Mol Biol Cell 15:447–455
Lu L, Hou X, Shi S, Körner C, Stanley P (2010) Slc35c2 promotes Notch1 fucosylation and is required for optimal Notch signaling in mammalian cells. J Biol Chem 285:36245–36254
Lübke T, Marquardt T, Etzioni A, Hartmann E, von Figura K, Körner C (2001) Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency. Nat Genet 28:73–76
Lübke T, Marquardt T, von Figura K, Körner C (1999) A new type of carbohydrate-deficient glycoprotein syndrome due to a decreased import of GDP-fucose into the golgi. J Biol Chem 274:25986–25989
Lühn K, Laskowska A, Pielage J, Klambt C, Ipe U, Vestweber D, Wild MK (2004) Identification and molecular cloning of a functional GDP-fucose transporter in Drosophila melanogaster. Exp Cell Res 301:242–250
Lühn K, Wild MK, Eckhardt M, Gerardy-Schahn R, Vestweber D (2001) The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. Nat Genet 28:69–72
Luo Y, Nita-Lazar A, Haltiwanger RS (2006) Two distinct pathways for O-fucosylation of epidermal growth factor-like or thrombospondin type 1 repeats. J Biol Chem 281:9385–9392
Marquardt T, Lühn K, Srikrishna G, Freeze HH, Harms E, Vestweber D (1999) Correction of leukocyte adhesion deficiency type II with oral fucose. Blood 94:3976–3985
Mayinger P, Meyer DI (1993) An ATP transporter is required for protein translocation into the yeast endoplasmic reticulum. EMBO J 12:659–666
Muraoka M, Miki T, Ishida N, Hara T, Kawakita M (2007) Variety of nucleotide sugar transporters with respect to the interaction with nucleoside mono- and diphosphates. J Biol Chem 282:24615–24622
Okajima T, Irvine KD (2002) Regulation of notch signaling by O-linked fucose. Cell 111:893–904
Perez M, Hirschberg CB (1987) Transport of sugar nucleotides into the lumen of vesicles derived from rat liver rough endoplasmic reticulum and Golgi apparatus. Methods Enzymol 138:709–715
Phillips ML, Schwartz BR, Etzioni A, Bayer R, Ochs HD, Paulson JC, Harlan JM (1995) Neutrophil adhesion in leukocyte adhesion deficiency syndrome type 2. J Clin Invest 96:2898–2906
Puglielli L, Hirschberg CB (1999) Reconstitution, identification, and purification of the rat liver golgi membrane GDP-fucose transporter. J Biol Chem 274:35596–35600
Seal RL, Gordon SM, Lush MJ, Wright MW, Bruford EA (2011) genenames.org: the HGNC resources in 2011. Nucleic Acids Res 39:D514–D519
Shi S, Stanley P (2003) Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways. Proc Natl Acad Sci USA 100:5234–5239
Sommers LW, Hirschberg CB (1982) Transport of sugar nucleotides into rat liver Golgi. A new Golgi marker activity. J Biol Chem 257:10811–10817
Sturla L, Etzioni A, Bisso A, Zanardi D, De Flora G, Silengo L, De Flora A, Tonetti M (1998) Defective intracellular activity of GDP-D-mannose-4,6-dehydratase in leukocyte adhesion deficiency type II syndrome. FEBS Lett 429:274–278
Sturla L, Puglielli L, Tonetti M, Berninsone P, Hirschberg CB, De Flora A, Etzioni A (2001) Impairment of the Golgi GDP-L-fucose transport and unresponsiveness to fucose replacement therapy in LAD II patients. Pediatr Res 49:537–542
Wild MK, Lühn K, Marquardt T, Vestweber D (2002) Leukocyte adhesion deficiency II: therapy and genetic defect. Cells Tissues Organs 172:161–173
Yakubenia S, Frommhold D, Schölch D, Hellbusch CC, Körner C, Petri B, Jones C, Ipe U, Bixel MG, Krempien R, Sperandio M, Wild MK (2008) Leukocyte trafficking in a mouse model for leukocyte adhesion deficiency II/congenital disorder of glycosylation IIc. Blood 112:1472–1481
Zhang P, Haryadi R, Chan KF, Teo G, Goh J, Pereira NA, Feng H, Song Z (2012) Identification of functional elements of the GDP-fucose transporter SLC35C1 using a novel Chinese hamster ovary mutant. Glycobiology 22:897–911
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Japan
About this entry
Cite this entry
Bakker, H., Ashikov, A., Routier, F.H., Gerardy-Schahn, R. (2014). GDP-Fucose Transporter 1 (SLC35C1). In: Taniguchi, N., Honke, K., Fukuda, M., Narimatsu, H., Yamaguchi, Y., Angata, T. (eds) Handbook of Glycosyltransferases and Related Genes. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54240-7_38
Download citation
DOI: https://doi.org/10.1007/978-4-431-54240-7_38
Published:
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-54239-1
Online ISBN: 978-4-431-54240-7
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences