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Endoplasmic Reticulum glycosylation

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    Dr. Hans Bakker

    Ph. D.

    Phone: +49(0)511/532-5214 or -9806

    FAX: +49(0)511/532-8801

    E-Mail: Bakker.Hans(at)mh-hannover.de

    Building J03, Level 04, Room 1290

RESEARCH

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    - C-mannosylation

     

    A thrombospondin type 1 repeat with two C-mannoses linked to tryptophan residues. The tryptophans are part of the tryptophan-arginine ladder that forms the heart of the thrombospondin repeat. The mannoses are transfered by specific endoplasmic reticulum localized C-mannosyltransferases of the DPY-19 family. The name DPY-19 comes from the worm C. elegans, where mutations in the C-mannosyltransferase gene lead to a temperature-sensitive DumPY phenotype.

     

    In humans there are four homologs of DPY-19, which are called DPY19L1, DPY19L2, DPY19L3, and DPY19L4.

     

     

     

     

     

    - Notch glycosylation

     

    - Glycolipid-specific glycosyltransferases

  • A thrombospondin type 1 repeat with two C-linked mannoses (green)

GROUP MEMBERS

Aleksandra Shcherbakova, Ph. D.

Jan Hütte, Ph. D. student

Hans Bakker, Group leader

Birgit Tiemann, Technician

LINKS

 

 DFG

 

 Lehre Biomembranes

PUBLICATIONS

 

Hoppe C. M., Albuquerque A., Bandini G., Leon D.R., Shcherbakova A., Buettner F.F.R., Izquierdo L., Costello C.E., Bakker H., Routier F. H., (2018), Apicomplexan C-Mannosyltransferases Modify Thrombospondin Type I-Containing Adhesins of the TRAP Family, Glycobiology, Feb 8. 

 

Bakker H, Gerardy-Schahn R, (2017), A sweet development in Notch regulation, J Biol Chem., Sep 22;292(38): 15974-15975.

 

Shcherbakova A., Tiemann B., Buettner F.F., Bakker H. (2017), Distinct C-mannosylation of netrin receptor thrombospondin type 1 repeats by mammalian DPY19L1 and DPY19L3. Proc Natl Acad Sci U S A. 114:2574-2579

 

Yu, H., Takeuchi, M., LeBarron, J., Kantharia, J., London, E., Bakker, H., Haltiwanger, R.S., Li, H., and Takeuchi, H. (2015). Notch-modifying xylosyltransferase structures support an Si-like retaining mechanism. Nat. Chem. Biol. 11, 847-854

 

Niemann, M.C., Bartrina, I., Ashikov, A., Weber, H., Novak, O., Spichal, L., Strnad, M., Strasser, R., Bakker, H., Schmulling, T., and Werner, T. (2015). Arabidopsis ROCK1 transports UDP-GlcNAc/UDP-GalNAc and regulates ER protein quality control and cytokinin activity. Proc. Natl Acad. Sci. U. S. A. 112, 291-296.

 

Bakker, H. (2014). Carbohydrate Sulfotransferase 10 (CHST10). Handbook of Glycosyltransferases and Related Genes 1035-1045.

 

Bakker, H. and Ashikov, A. (2014). UDP-Xylose and UDP-N-Acetylglucosamine Transporter (SLC35B4). Handbook of Glycosyltransferases and Related Genes 1393-1402.

 

Bakker, H. (2014). UDP-Glucuronate Decarboxylase 1 (UXS1). Handbook of Glycosyltransferases and Related Genes 1439-1448.

 

Bakker, H., Ashikov, A., Routier, F.H., and Gerardy-Schahn, R. (2014). GDP-Fucose Transporter 1 (SLC35C1). Handbook of Glycosyltransferases and Related Genes 1403-1411.

 

Buettner, F.F., Ashikov, A., Tiemann, B., Lehle, L., and Bakker, H. (2013). C. elegans DPY-19 is a C-Mannosyltransferase Glycosylating Thrombospondin Repeats. Mol. Cell 50, 295-302.

 

Lee, T.V., Sethi, M.K., Leonardi, J., Rana, N.A., Buettner, F.F., Haltiwanger, R.S., Bakker, H., and Jafar-Nejad, H. (2013). Negative Regulation of Notch Signaling by Xylose. PLoS genetics 9, e1003547.

 

Sethi,M.K., Buettner,F.F., Ashikov,A., and Bakker,H. (2013). In Vitro Assays of Orphan Glycosyltransferases and Their Application to Identify Notch Xylosyltransferases. Methods Mol Biol., 1022, 307-320.

 

Ashikov,A., Buettner, FF., Tiemann, B., Gerardy-Schahn, R., and Bakker, H. (2013) LARGE2 generates the same xylose and glucuronic acid containing glycan structures as LARGE. Glycobiology 23, 303-309.

 

Sethi,M.K., Buettner,F.F., Ashikov,A., Krylov,V.B., Takeuchi,H., Nifantiev,N.E., Haltiwanger,R.S., Gerardy-Schahn,R., and Bakker,H. (2012). Molecular Cloning of a Xylosyltransferase that Transfers the Second Xylose to O-Glucosylated Epidermal Growth Factor Repeats of Notch. J. Biol. Chem. 287, 2739-2748.

 

Kraft,B., Johswich,A., Kauczor,G., Scharenberg,M., Gerardy-Schahn,R., and Bakker,H. (2011). "Add-on" domains of Drosophila beta1,4-N-acetylgalactosaminyltransferase B in the stem region and its pilot protein. Cell Mol. Life Sci., 68, 4091-4100.

 

Sethi,M.K., Buettner,F.F., Krylov,V.B., Takeuchi,H., Nifantiev,N.E., Haltiwanger,R.S., Gerardy-Schahn,R., and Bakker,H. (2010). Identification of glycosyltransferase 8 family members as xylosyltransferases acting on O-glucosylated notch epidermal growth factor repeats. J. Biol. Chem., 285, 1582-1586.

 

Bakker,H., Oka,T., Ashikov,A., Yadav,A., Berger,M., Rana,N.A., Bai,X., Jigami,Y., Haltiwanger,R.S., Esko,J.D., and Gerardy-Schahn,R. (2009). Functional UDP-xylose transport across the endoplasmic reticulum/Golgi membrane in a Chinese hamster ovary cell mutant defective in UDP-xylose Synthase. J. Biol. Chem., 284, 2576-2583.

 

Boztug,K., Appaswamy,G., Ashikov,A., Schaffer,A.A., Salzer,U., Diestelhorst,J., Germeshausen,M., Brandes,G., Lee-Gossler,J., Noyan,F., Gatzke,A.K., Minkov,M., Greil,J., Kratz,C., Petropoulou,T., Pellier,I., Bellanne-Chantelot,C., Rezaei,N., Monkemoller,K., Irani-Hakimeh,N., Bakker,H., Gerardy-Schahn,R., Zeidler,C., Grimbacher,B., Welte,K., and Klein,C. (2009). A syndrome with congenital neutropenia and mutations in G6PC3. N. Engl. J. Med., 360, 32-43.

 

Johswich,A., Kraft,B., Wuhrer,M., Berger,M., Deelder,A.M., Hokke,C.H., Gerardy-Schahn,R., and Bakker,H. (2009). Golgi targeting of Drosophila melanogaster beta4GalNAcTB requires a DHHC protein family-related protein as a pilot. J. Cell Biol., 184, 173-183.

 

Bakker,H., Routier,F., Ashikov,A., Neumann,D., Bosch,D., and Gerardy-Schahn,R. (2008). A CMP-sialic acid transporter cloned from Arabidopsis thaliana. Carbohydr. Res., 343, 2148-2152.

 

Caffaro,C.E., Luhn,K., Bakker,H., Vestweber,D., Samuelson,J., Berninsone,P., and Hirschberg,C.B. (2008). A single Caenorhabditis elegans Golgi apparatus-type transporter of UDP-glucose, UDP-galactose, UDP-N-acetylglucosamine, and UDP-N-acetylgalactosamine. Biochemistry, 47, 4337-4344.

 

Schmalhorst,P.S., Krappmann,S., Vervecken,W., Rohde,M., Muller,M., Braus,G.H., Contreras,R., Braun,A., Bakker,H., and Routier,F.H. (2008). Contribution of galactofuranose to the virulence of the opportunistic pathogen Aspergillus fumigatus. Eukaryot. Cell, 7, 1268-1277.

 

Stolz,A., Haines,N., Pich,A., Irvine,K.D., Hokke,C.H., Deelder,A.M., Gerardy-Schahn,R., Wuhrer,M., and Bakker,H. (2008). Distinct contributions of beta 4GalNAcTA and beta 4GalNAcTB to Drosophila glycosphingolipid biosynthesis. Glycoconj. J., 25, 167-175.

 

Kleczka,B., Lamerz,A.C., van Zandbergen,G., Wenzel,A., Gerardy-Schahn,R., Wiese,M., and Routier,F.H. (2007). Targeted gene deletion of Leishmania major UDP-galactopyranose mutase leads to attenuated virulence. J. Biol. Chem., 282, 10498-10505.

 

Krylov,V., Ustyuzhanina,N., Grachev,A., Bakker,H., and Nifantiev,N. (2007). Stereoselective synthesis of the 3-aminopropyl glycosides of a-D-Xyl-(1 -> 3)b-D-Glc and a-D-Xyl-(1 -> 3)-a-D-Xyl-(1 -> 3)-b-D-Glc and of their corresponding N-octanoyl derivatives. Synthesis, 2007, 3147-3154.

 

Rouwendal,G.J., Wuhrer,M., Florack,D.E., Koeleman,C.A., Deelder,A.M., Bakker,H., Stoopen,G.M., van,D., I, Helsper,J.P., Hokke,C.H., and Bosch,D. (2007). Efficient introduction of a bisecting GlcNAc residue in tobacco N-glycans by expression of the gene encoding human N-acetylglucosaminyltransferase III. Glycobiology, 17, 334-344.

 

Bakker,H., Rouwendal,G.J., Karnoup,A.S., Florack,D.E., Stoopen,G.M., Helsper,J.P., van Ree,R., van,D., I, and Bosch,D. (2006). An antibody produced in tobacco expressing a hybrid beta-1,4-galactosyltransferase is essentially devoid of plant carbohydrate epitopes. Proc. Natl. Acad. Sci. U. S. A, 103, 7577-7582.

 

Tiralongo,J., Ashikov,A., Routier,F., Eckhardt,M., Bakker,H., Gerardy-Schahn,R., and von Itzstein,M. (2006). Functional expression of the CMP-sialic acid transporter in Escherichia coli and its identification as a simple mobile carrier. Glycobiology, 16, 73-81.

 

Ashikov,A., Routier,F., Fuhlrott,J., Helmus,Y., Wild,M., Gerardy-Schahn,R., and Bakker,H. (2005). The human solute carrier gene SLC35B4 encodes a bifunctional nucleotide sugar transporter with specificity for UDP-xylose and UDP-N-acetylglucosamine. J. Biol. Chem., 280, 27230-27235.

 

Bakker,H., Kleczka,B., Gerardy-Schahn,R., and Routier,F.H. (2005). Identification and partial characterization of two eukaryotic UDP-galactopyranose mutases. Biol. Chem., 386, 657-661.

 

Bakker,H., Routier,F., Oelmann,S., Jordi,W., Lommen,A., Gerardy-Schahn,R., and Bosch,D. (2005). Molecular cloning of two Arabidopsis UDP-galactose transporters by complementation of a deficient Chinese hamster ovary cell line. Glycobiology, 15, 193-201.

 

Kabuss,R., Ashikov,A., Oelmann,S., Gerardy-Schahn,R., and Bakker,H. (2005). ER retention of the large splice variant of the UDP-galactose transporter is caused by a di-lysine motif. Glycobiology.

 

Bakker,H., Schijlen,E., de Vries,T., Schiphorst,W.E., Jordi,W., Lommen,A., Bosch,D., and van,D., I (2001). Plant members of the alpha1-->3/4-fucosyltransferase gene family encode an alpha1-->4-fucosyltransferase, potentially involved in Lewis(a) biosynthesis, and two core alpha1-->3-fucosyltransferases. FEBS Lett., 507, 307-312.

 

Bakker,H., Bardor,M., Molthoff,J.W., Gomord,V., Elbers,I., Stevens,L.H., Jordi,W., Lommen,A., Faye,L., Lerouge,P., and Bosch,D. (2001). Galactose-extended glycans of antibodies produced by transgenic plants. Proc. Natl. Acad. Sci. U. S. A, 98, 2899-2904.

 

Elbers,I.J., Stoopen,G.M., Bakker,H., Stevens,L.H., Bardor,M., Molthoff,J.W., Jordi,W.J., Bosch,D., and Lommen,A. (2001). Influence of growth conditions and developmental stage on N-glycan heterogeneity of transgenic immunoglobulin G and endogenous proteins in tobacco leaves. Plant Physiol, 126, 1314-1322.

 

Gerardy-Schahn,R., Oelmann,S., and Bakker,H. (2001). Nucleotide sugar transporters: biological and functional aspects. Biochimie, 83, 775-782.

 

Stevens,L.H., Stoopen,G.M., Elbers,I.J., Molthoff,J.W., Bakker,H.A., Lommen,A., Bosch,D., and Jordi,W. (2000). Effect of climate conditions and plant developmental stage on the stability of antibodies expressed in transgenic tobacco. Plant Physiol, 124, 173-182.

 

Bakker,H., Lommen,A., Jordi,W., Stiekema,W., and Bosch,D. (1999). An Arabidopsis thaliana cDNA complements the N-acetylglucosaminyltransferase I deficiency of CHO Lec1 cells. Biochem. Biophys. Res. Commun., 261, 829-832.

 

Sato,T., Furukawa,K., Bakker,H., Van den Eijnden,D.H., and van,D., I (1998). Molecular cloning of a human cDNA encoding beta-1,4-galactosyltransferase with 37% identity to mammalian UDP-Gal:GlcNAc beta-1,4-galactosyltransferase. Proc. Natl. Acad. Sci. U. S. A, 95, 472-477.

 

Van den Eijnden,D.H., Neeleman,A.P., Bakker,H., and van,D., I (1998). Novel pathways in complex-type oligosaccharide synthesis. New vistas opened by studies in invertebrates. Adv. Exp. Med. Biol., 435, 3-7.

 

Bakker,H., Van Tetering,A., Agterberg,M., Smit,A.B., Van den Eijnden,D.H., and van Die,I. (1997). Deletion of two exons from the Lymnaea stagnalis beta1-->4-N-acetylglucosaminyltransferase gene elevates the kinetic efficiency of the encoded enzyme for both UDP-sugar donor and acceptor substrates. J. Biol. Chem., 272, 18580-18585.

 

Bakker,H., Schoenmakers,P.S., Koeleman,C.A., Joziasse,D.H., van Die,I., and Van den Eijnden,D.H. (1997). The substrate specificity of the snail Lymnaea stagnalis UDP-GlcNAc:GlcNAc beta-R beta 4-N-acetylglucosaminyltransferase reveals a novel variant pathway of complex-type oligosaccharide synthesis. Glycobiology, 7, 539-548.

 

Bakker,H., Friedmann,I., Oka,S., Kawasaki,T., Nifant'ev,N., Schachner,M., and Mantei,N. (1997). Expression cloning of a cDNA encoding a sulfotransferase involved in the biosynthesis of the HNK-1 carbohydrate epitope. J. Biol. Chem., 272, 29942-29946.

 

Van den Eijnden,D.H., Bakker,H., Neeleman,A.P., Van den Nieuwenhof,I., and van Die,I. (1997). Novel pathways in complex-type oligosaccharide synthesis: new vistas opened by studies in invertebrates. Biochem. Soc. Trans., 25, 887-893.

 

van Die,I., Bakker,H., and Van den Eijnden,D.H. (1997). Identification of conserved amino acid motifs in members of the beta1-->4-galactosyltransferase gene family. Glycobiology, 7, v-viii.

 

van Die,I., Van Tetering,A., Bakker,H., Van den Eijnden,D.H., and Joziasse,D.H. (1996). Glycosylation in lepidopteran insect cells: identification of a beta 1-->4-N-acetylgalactosaminyltransferase involved in the synthesis of complex-type oligosaccharide chains. Glycobiology, 6, 157-164.

 

Van den Eijnden,D.H., Neeleman,A.P., Van der Knaap,W.P., Bakker,H., Agterberg,M., and van Die,I. (1995). Control and function of complex-type oligosaccharide synthesis. Novel variants of the lacNAc pathway. Adv. Exp. Med. Biol., 376, 47-52.

 

Van den Eijnden,D.H., Neeleman,A.P., Van der Knaap,W.P., Bakker,H., Agterberg,M., and van Die,I. (1995). Novel glycosylation routes for glycoproteins: the lacdiNAc pathway. Biochem. Soc. Trans., 23, 175-179.

 

Bakker,H., Agterberg,M., Van Tetering,A., Koeleman,C.A., Van den Eijnden,D.H., and van Die,I. (1994). A Lymnaea stagnalis gene, with sequence similarity to that of mammalian beta 1-->4-galactosyltransferases, encodes a novel UDP-GlcNAc:GlcNAc beta-R beta 1-->4-N-acetylglucosaminyltransferase. J. Biol. Chem., 269, 30326-30333.

 

de Boer,D., Bakker,H., Lever,A., Bouma,T., Salentijn,E., and Weisbeek,P. (1991). Protein targeting towards the thylakoid lumen of chloroplasts: proper localization of fusion proteins is only observed in vivo. EMBO J., 10, 2765-2772.