Skip to main content

Advertisement

SpringerLink
Log in

The N’s and O’s of Drosophila glycoprotein glycobiology

  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

The past 25 years have seen significant advances in understanding the diversity and functions of glycoprotein glycans in Drosophila melanogaster. Genetic screens have captured mutations that reveal important biological activities modulated by glycans, including protein folding and trafficking, as well as cell signaling, tissue morphogenesis, fertility, and viability. Many of these glycan functions have parallels in vertebrate development and disease, providing increasing opportunities to dissect pathologic mechanisms using Drosophila genetics. Advances in the sensitivity of structural analytic techniques have allowed the glycan profiles of wild-type and mutant tissues to be assessed, revealing novel glycan structures that may be functionally analogous to vertebrate glycans. This review describes a selected set of recent advances in understanding the functions of N-linked and O-linked (non-glycosaminoglycan) glycoprotein glycans in Drosophila with emphasis on their relatedness to vertebrate organisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Lin, X.: Functions of heparan sulfate proteoglycans in cell signaling during development. Development 131(24), 6009–6021 (2004). doi:10.1242/dev.01522

    Article  PubMed  CAS  Google Scholar 

  2. Selleck, S.B.: Genetic dissection of proteoglycan function in Drosophila and C. elegans. Semin. Cell Dev. Biol. 12(2), 127–134 (2001). doi:10.1006/scdb.2000.0242

    Article  PubMed  CAS  Google Scholar 

  3. Chen, Y.W., Pedersen, J.W., Wandall, H.H., Levery, S.B., Pizette, S., Clausen, H., Cohen, S.M.: Glycosphingolipids with extended sugar chain have specialized functions in development and behavior of Drosophila. Dev. Biol. 306(2), 736–749 (2007). doi:10.1016/j.ydbio.2007.04.013

    Article  PubMed  CAS  Google Scholar 

  4. Dahlgaard, K., Jung, A., Qvortrup, K., Clausen, H., Kjaerulff, O., Wandall, H.H.: Neurofibromatosis-like phenotype in Drosophila caused by lack of glucosylceramide extension. Proc. Natl. Acad. Sci. U. S. A. (2012). doi:10.1073/pnas.1115453109

  5. Muller, R., Altmann, F., Zhou, D., Hennet, T.: The Drosophila melanogaster brainiac protein is a glycolipid-specific beta 1,3 N-acetylglucosaminyltransferase. J. Biol. Chem. 277(36), 32417–32420 (2002). doi:10.1074/jbc.C200381200

    Article  PubMed  Google Scholar 

  6. Pizette, S., Rabouille, C., Cohen, S.M., Therond, P.: Glycosphingolipids control the extracellular gradient of the Drosophila EGFR ligand Gurken. Development 136(4), 551–561 (2009). doi:10.1242/dev.031104

    Article  PubMed  CAS  Google Scholar 

  7. Schwientek, T., Keck, B., Levery, S.B., Jensen, M.A., Pedersen, J.W., Wandall, H.H., Stroud, M., Cohen, S.M., Amado, M., Clausen, H.: The Drosophila gene brainiac encodes a glycosyltransferase putatively involved in glycosphingolipid synthesis. J. Biol. Chem. 277(36), 32421–32429 (2002). doi:10.1074/jbc.M206213200

    Article  PubMed  CAS  Google Scholar 

  8. Seppo, A., Moreland, M., Schweingruber, H., Tiemeyer, M.: Zwitterionic and acidic glycosphingolipids of the Drosophila melanogaster embryo. Eur. J. Biochem. FEBS 267(12), 3549–3558 (2000)

    Article  CAS  Google Scholar 

  9. Seppo, A., Tiemeyer, M.: Function and structure of Drosophila glycans. Glycobiology 10(8), 751–760 (2000)

    Article  PubMed  CAS  Google Scholar 

  10. Stolz, A., Haines, N., Pich, A., Irvine, K.D., Hokke, C.H., Deelder, A.M., Gerardy-Schahn, R., Wuhrer, M., Bakker, H.: Distinct contributions of beta 4GalNAcTA and beta 4GalNAcTB to Drosophila glycosphingolipid biosynthesis. Glycoconj. J. 25(2), 167–175 (2008). doi:10.1007/s10719-007-9069-5

    Article  PubMed  CAS  Google Scholar 

  11. Wandall, H.H., Pedersen, J.W., Park, C., Levery, S.B., Pizette, S., Cohen, S.M., Schwientek, T., Clausen, H.: Drosophila egghead encodes a beta 1,4-mannosyltransferase predicted to form the immediate precursor glycosphingolipid substrate for brainiac. J. Biol. Chem. 278(3), 1411–1414 (2003). doi:10.1074/jbc.C200619200

    Article  PubMed  CAS  Google Scholar 

  12. Wandall, H.H., Pizette, S., Pedersen, J.W., Eichert, H., Levery, S.B., Mandel, U., Cohen, S.M., Clausen, H.: Egghead and brainiac are essential for glycosphingolipid biosynthesis in vivo. J. Biol. Chem. 280(6), 4858–4863 (2005). doi:10.1074/jbc.C400571200

    Article  PubMed  CAS  Google Scholar 

  13. Park, S., Park, S.H., Baek, J.Y., Jy, Y.J., Kim, K.S., Roth, J., Cho, J.W., Choe, K.M.: Protein O-GlcNAcylation regulates Drosophila growth through the insulin signaling pathway. Cell Mol. Life Sci. CMLS 68(20), 3377–3384 (2011). doi:10.1007/s00018-011-0640-7

    Article  CAS  Google Scholar 

  14. Sekine, O., Love, D.C., Rubenstein, D.S., Hanover, J.A.: Blocking O-linked GlcNAc cycling in Drosophila insulin-producing cells perturbs glucose-insulin homeostasis. J. Biol. Chem. 285(49), 38684–38691 (2010). doi:10.1074/jbc.M110.155192

    Article  PubMed  CAS  Google Scholar 

  15. Aoki, K., Perlman, M., Lim, J.M., Cantu, R., Wells, L., Tiemeyer, M.: Dynamic developmental elaboration of N-linked glycan complexity in the Drosophila melanogaster embryo. J. Biol. Chem. 282(12), 9127–9142 (2007). doi:10.1074/jbc.M606711200

    Article  PubMed  CAS  Google Scholar 

  16. Aoki, K., Tiemeyer, M.: The glycomics of glycan glucuronylation in Drosophila melanogaster. Methods Enzymol. 480, 297–321 (2010). doi:10.1016/S0076-6879(10)80014-X

    Article  PubMed  CAS  Google Scholar 

  17. North, S.J., Koles, K., Hembd, C., Morris, H.R., Dell, A., Panin, V.M., Haslam, S.M.: Glycomic studies of Drosophila melanogaster embryos. Glycoconj. J. 23(5–6), 345–354 (2006). doi:10.1007/s10719-006-6693-4

    Article  PubMed  CAS  Google Scholar 

  18. ten Hagen, K.G., Zhang, L., Tian, E., Zhang, Y.: Glycobiology on the fly: developmental and mechanistic insights from Drosophila. Glycobiology 19(2), 102–111 (2009). doi:10.1093/glycob/cwn096

    Article  PubMed  CAS  Google Scholar 

  19. Helenius, A., Aebi, M.: Roles of N-linked glycans in the endoplasmic reticulum. Annu. Rev. Biochem. 73, 1019–1049 (2004). doi:10.1146/annurev.biochem.73.011303.073752

    Article  PubMed  CAS  Google Scholar 

  20. Helenius, A., Aebi, M.: Intracellular functions of N-linked glycans. Science 291(5512), 2364–2369 (2001)

    Article  PubMed  CAS  Google Scholar 

  21. Hargrave, P.A.: The amino-terminal tryptic peptide of bovine rhodopsin. A glycopeptide containing two sites of oligosaccharide attachment. Biochim. Biophys. Acta. 492(1), 83–94 (1977)

    Article  PubMed  CAS  Google Scholar 

  22. Murray, A.R., Fliesler, S.J., Al-Ubaidi, M.R.: Rhodopsin: the functional significance of asn-linked glycosylation and other post-translational modifications. Ophthalmic Genet 30(3), 109–120 (2009). doi:10.1080/13816810902962405

    Article  PubMed  CAS  Google Scholar 

  23. Dryja, T.P., Li, T.: Molecular genetics of retinitis pigmentosa. Hum. Mol. Genet 4, 1739–1743 (1995)

    PubMed  CAS  Google Scholar 

  24. Webel, R., Menon, I., O’Tousa, J.E., Colley, N.J.: Role of asparagine-linked oligosaccharides in rhodopsin maturation and association with its molecular chaperone, NinaA. J. Biol. Chem. 275(32), 24752–24759 (2000). doi:10.1074/jbc.M002668200

    Article  PubMed  CAS  Google Scholar 

  25. Katanosaka, K., Tokunaga, F., Kawamura, S., Ozaki, K.: N-linked glycosylation of Drosophila rhodopsin occurs exclusively in the amino-teminal domain and function in rhodopsin maturation. FEBS Lett. 424, 149–154 (1998)

    Article  PubMed  CAS  Google Scholar 

  26. Satoh, A., Tokunaga, F., Kawamura, S., Ozaki, K.: In situ inhibition of vesicle transport and protein processing in the dominant negative Rab1 mutant of Drosophila. J. Cell Sci. 110(Pt 23), 2943–2953 (1997)

    PubMed  CAS  Google Scholar 

  27. Cao, J., Li, Y., Xia, W., Reddig, K., Hu, W., Xie, W., Li, H.S., Han, J.: A Drosophila metallophosphoesterase mediates deglycosylation of rhodopsin. EMBO J. 30(18), 3701–3713 (2011). doi:10.1038/emboj.2011.254

    Article  PubMed  CAS  Google Scholar 

  28. Suzuki, T., Park, H., Hollingsworth, N.M., Sternglanz, R., Lennarz, W.J.: PNG1, a yeast gene encoding a highly conserved peptide:N-glycanase. J. Cell Biol. 149(5), 1039–1052 (2000)

    Article  PubMed  CAS  Google Scholar 

  29. Suzuki, T.: Cytoplasmic peptide:N-glycanase and catabolic pathway for free N-glycans in the cytosol. Semin Cell Dev. Biol. 18(6), 762–769 (2007). doi:10.1016/j.semcdb.2007.09.010

    Article  PubMed  CAS  Google Scholar 

  30. Spiro, R.G.: Role of N-linked polymannose oligosaccharides in targeting glycoproteins for endoplasmic reticulum-associated degradation. Cell Mol Life Sci, CMLS 61(9), 1025–1041 (2004). doi:10.1007/s00018-004-4037-8

    Article  CAS  Google Scholar 

  31. Altrich-VanLith, M.L., Ostankovitch, M., Polefrone, J.M., Mosse, C.A., Shabanowitz, J., Hunt, D.F., Engelhard, V.H.: Processing of a class I-restricted epitope from tyrosinase requieres peptide N-glycanase and the cooperative action of endoplasmic reticulum aminopeptidase 1 and cytosolic protease. J. Immunol. (2006).

  32. Kario, E., Tirosh, B., Ploegh, H.L., Navon, A.: N-linked glycosylation does not impair proteasomal degradation but affects class I major histocompatibility complex presentation. J. Biol. Chem. 283(1), 244–254 (2008). doi:10.1074/jbc.M706237200

    Article  PubMed  CAS  Google Scholar 

  33. Funakoshi, Y., Negishi, Y., Gengen, J.P., Seino, J., Ishii, K., Lennarz, W.J., Matsuo, I., Ito, Y., Taniguchi, N., Suzuki, T.: Evidence for an Essential Deglycosylation-Independent Activity of PNGase in Drosophila melanogaster. PLoS One 5(5), e10545 (2010). doi:10.1371/journal.pone.0010545.g001

    Article  PubMed  CAS  Google Scholar 

  34. Leonard, R., Rendic, D., Rabouille, C., Wilson, I.B., Preat, T., Altmann, F.: The Drosophila fused lobes gene encodes an N-acetylglucosaminidase involved in N-glycan processing. J. Biol. Chem. 281(8), 4867–4875 (2006). doi:10.1074/jbc.M511023200

    Article  PubMed  CAS  Google Scholar 

  35. Geisler, C., Aumiller, J.J., Jarvis, D.L.: A fused lobes gene encodes the processing beta-N-acetylglucosaminidase in Sf9 cells. J. Biol. Chem. 283(17), 11330–11339 (2008). doi:10.1074/jbc.M710279200

    Article  PubMed  CAS  Google Scholar 

  36. Boquet, I., Hitier, R., Dumas, M., Chaminade, M., Preat, T.: Central brain postembryonic development in Drosophila: implication of genes expressed at the interhemispheric junction. J. Neurobiol. 42(1), 33–48 (2000)

    Article  PubMed  CAS  Google Scholar 

  37. Sarkar, M., Leventis, P.A., Silvescu, C.I., Reinhold, V.N., Schachter, H., Boulianne, G.L.: Null mutations in Drosophila N-acetylglucosaminyltransferase I produce defects in locomotion and a reduced life span. J. Biol. Chem. 281(18), 12776–12785 (2006). doi:10.1074/jbc.M512769200

    Article  PubMed  CAS  Google Scholar 

  38. Sarkar, M., Iliadi, K.G., Leventis, P.A., Schachter, H., Boulianne, G.L.: Neuronal expression of Mgat1 rescues the shortened life span of Drosophila Mgat11 null mutants and increases life span. Proc. Natl. Acad. Sci. U. S. A. 107(21), 9677–9682 (2010). doi:10.1073/pnas.1004431107

    Article  PubMed  Google Scholar 

  39. Fredieu, J.R., Mahowald, A.P.: Glycoconjugate expression during Drosophila embryogenesis. Acta anatomica 149(2), 89–99 (1994)

    Article  PubMed  CAS  Google Scholar 

  40. Williams, P.J., Wormald, M.R., Dwek, R.A., Rademacher, T.W., Parker, G.F., Roberts, D.R.: Characterisation of oligosaccharides from Drosophila melanogaster glycoproteins. Biochim. Biophys. Acta 1075(2), 146–153 (1991)

    Article  PubMed  CAS  Google Scholar 

  41. Nakamura, Y., Haines, N., Chen, J., Okajima, T., Furukawa, K., Urano, T., Stanley, P., Irvine, K.D., Furukawa, K.: Identification of a Drosophila gene encoding xylosylprotein beta4-galactosyltransferase that is essential for the synthesis of glycosaminoglycans and for morphogenesis. J. Biol. Chem. 277(48), 46280–46288 (2002). doi:10.1074/jbc.M203873200

    Article  PubMed  CAS  Google Scholar 

  42. Takemae, H., Ueda, R., Okubo, R., Nakato, H., Izumi, S., Saigo, K., Nishihara, S.: Proteoglycan UDP-galactose:beta-xylose beta 1,4-galactosyltransferase I is essential for viability in Drosophila melanogaster. J. Biol. Chem. 278(18), 15571–15578 (2003). doi:10.1074/jbc.M301123200

    Article  PubMed  CAS  Google Scholar 

  43. Vadaie, N., Hulinsky, R.S., Jarvis, D.L.: Identification and characterization of a Drosophila melanogaster ortholog of human beta1,4-galactosyltransferase VII. Glycobiology 12(10), 589–597 (2002)

    Article  PubMed  CAS  Google Scholar 

  44. Haines, N., Irvine, K.D.: Functional analysis of Drosophila beta1,4-N-acetlygalactosaminyltransferases. Glycobiology 15(4), 335–346 (2005). doi:10.1093/glycob/cwi017

    Article  PubMed  Google Scholar 

  45. Sasaki, N., Yoshida, H., Fuwa, T.J., Kinoshita-Toyoda, A., Toyoda, H., Hirabayashi, Y., Ishida, H., Ueda, R., Nishihara, S.: Drosophila beta 1,4-N-acetylgalactosaminyltransferase-A synthesizes the LacdiNAc structures on several glycoproteins and glycosphingolipids. Biochem. Biophys. Res. Commun. 354(2), 522–527 (2007). doi:10.1016/j.bbrc.2007.01.015

    Article  PubMed  CAS  Google Scholar 

  46. Ramakrishnan, B., Qasba, P.K.: Role of a single amino acid in the evolution of glycans of invertebrates and vertebrates. J. Mol. Biol. 365(3), 570–576 (2007). doi:10.1016/j.jmb.2006.10.034

    Article  PubMed  CAS  Google Scholar 

  47. Johswich, A., Kraft, B., Wuhrer, M., Berger, M., Deelder, A.M., Hokke, C.H., Gerardy-Schahn, R., Bakker, H.: Golgi targeting of Drosophila melanogaster beta4GalNAcTB requires a DHHC protein family-related protein as a pilot. J Cell Biol 184(1), 173–183 (2009). doi:10.1083/jcb.200801071

    Article  PubMed  CAS  Google Scholar 

  48. Koles, K., Irvine, K.D., Panin, V.M.: Functional characterization of Drosophila sialyltransferase. J. Biol. Chem. 279(6), 4346–4357 (2004). doi:10.1074/jbc.M309912200

    Article  PubMed  CAS  Google Scholar 

  49. Repnikova, E., Koles, K., Nakamura, M., Pitts, J., Li, H., Ambavane, A., Zoran, M.J., Panin, V.M.: Sialyltransferase regulates nervous system function in Drosophila. J. Neurosci. 30(18), 6466–6476 (2010). doi:10.1523/JNEUROSCI.5253-09.2010

    Article  PubMed  CAS  Google Scholar 

  50. Ripoche, J., Link, B., Yucel, J.K., Tokuyasu, K., Malhotra, V.: Location of Golgi membranes with reference to dividing nuclei in syncytial Drosophila embryos. Proc. Natl. Acad. Sci. U. S. A. 91(5), 1878–1882 (1994)

    Article  PubMed  CAS  Google Scholar 

  51. Yamamoto-Hino, M., Abe, M., Shibano, T., Setoguchi, Y., Awano, W., Ueda, R., Okano, H., Goto, S.: Cisterna-specific Localization of Glycosylation-related Proteins to the Golgi Apparatus. Cell. Struct. Funct. 37(1), 55–63 (2012)

    Article  PubMed  Google Scholar 

  52. Yano, H., Yamamoto-Hino, M., Abe, M., Kuwahara, R., Haraguchi, S., Kusaka, I., Awano, W., Kinoshita-Toyoda, A., Toyoda, H., Goto, S.: Distinct functional units of the Golgi complex in Drosophila cells. Proc. Natl. Acad. Sci. U. S. A. 102(38), 13467–13472 (2005). doi:10.1073/pnas.0506681102

    Article  PubMed  CAS  Google Scholar 

  53. Yamamoto-Hino, M., Kanie, Y., Awano, W., Aoki-Kinoshita, K.F., Yano, H., Nishihara, S., Okano, H., Ueda, R., Kanie, O., Goto, S.: Identification of genes required for neural-specific glycosylation using functional genomics. PLoS Genet 6(12), e1001254 (2010). doi:10.1371/journal.pgen.1001254

    Article  PubMed  CAS  Google Scholar 

  54. Baas, S., Sharrow, M., Kotu, V., Middleton, M., Nguyen, K., Flanagan-Steet, H., Aoki, K., Tiemeyer, M.: Sugar-free frosting, a homolog of SAD kinase, drives neural-specific glycan expression in the Drosophila embryo. Development 138(3), 553–563 (2011). doi:10.1242/dev.055376

    Article  PubMed  CAS  Google Scholar 

  55. Farhan, H., Wendeler, M.W., Mitrovic, S., Fava, E., Silberberg, Y., Sharan, R., Zerial, M., Hauri, H.P.: MAPK signaling to the early secretory pathway revealed by kinase/phosphatase functional screening. J. Cell Biol. 189(6), 997–1011 (2010). doi:10.1083/jcb.200912082

    Article  PubMed  CAS  Google Scholar 

  56. Lowe, M., Rabouille, C., Nakamura, N., Watson, R., Jackman, M., Jamsa, E., Rahman, D., Pappin, D.J., Warren, G.: Cdc2 kinase directly phosphorylates the cis-Golgi matrix protein GM130 and is required for Golgi fragmentation in mitosis. Cell 94(6), 783–793 (1998)

    Article  PubMed  CAS  Google Scholar 

  57. Snow, P.M., Patel, N.H., Harrelson, A.L., Goodman, C.S.: Neural-specific carbohydrate moiety shared by many surface glycoproteins in Drosophila and grasshopper embryos. J. Neurosci. 7(12), 4137–4144 (1987)

    PubMed  CAS  Google Scholar 

  58. Kramerov, A.A., Arbatsky, N.P., Rozovsky, Y.M., Mikhaleva, E.A., Polesskaya, O.O., Gvozdev, V.A., Shibaev, V.N.: Mucin-type glycoprotein from Drosophila melanogaster embryonic cells: characterization of carbohydrate component. FEBS Lett. 378(3), 213–218 (1996)

    Article  PubMed  CAS  Google Scholar 

  59. Kramerov, A.A., Mikhaleva, E.A., Rozovsky Ya, M., Pochechueva, T.V., Baikova, N.A., Arsenjeva, E.L., Gvozdev, V.A.: Insect mucin-type glycoprotein: immunodetection of the O-glycosylated epitope in Drosophila melanogaster cells and tissues. Insect Biochem. Mol. Biol. 27(6), 513–521 (1997)

    Article  PubMed  CAS  Google Scholar 

  60. Haines, N., Irvine, K.D.: Glycosylation regulates Notch signalling. Nat. Rev. Mol. Cell Biol. 4(10), 786–797 (2003). doi:10.1038/nrm1228

    Article  PubMed  CAS  Google Scholar 

  61. Theopold, U., Dorian, C., Schmidt, O.: Changes in glycosylation during Drosophila development. The influence of ecdysone on hemomucin isoforms. Insect Biochem. Mol. Biol. 31(2), 189–197 (2001)

    Article  PubMed  CAS  Google Scholar 

  62. Tian, E., Ten Hagen, K.G.: Expression of the UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase family is spatially and temporally regulated during Drosophila development. Glycobiology 16(2), 83–95 (2006). doi:10.1093/glycob/cwj051

    Article  PubMed  CAS  Google Scholar 

  63. Tian, E., Ten Hagen, K.G.: O-linked glycan expression during Drosophila development. Glycobiology 17(8), 820–827 (2007). doi:10.1093/glycob/cwm056

    Article  PubMed  CAS  Google Scholar 

  64. Okajima, T., Xu, A., Irvine, K.D.: Modulation of notch-ligand binding by protein O-fucosyltransferase 1 and fringe. J. Biol. Chem. 278(43), 42340–42345 (2003). doi:10.1074/jbc.M308687200

    Article  PubMed  CAS  Google Scholar 

  65. Haltiwanger, R.S., Stanley, P.: Modulation of receptor signaling by glycosylation: fringe is an O-fucose-beta1,3-N-acetylglucosaminyltransferase. Biochim. Biophys. Acta 1573(3), 328–335 (2002)

    Article  PubMed  CAS  Google Scholar 

  66. Moloney, D.J., Panin, V.M., Johnston, S.H., Chen, J., Shao, L., Wilson, R., Wang, Y., Stanley, P., Irvine, K.D., Haltiwanger, R.S., Vogt, T.F.: Fringe is a glycosyltransferase that modifies Notch. Nature 406(6794), 369–375 (2000). doi:10.1038/35019000

    Article  PubMed  CAS  Google Scholar 

  67. Tian, E., Ten Hagen, K.G.: A UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase is required for epithelial tube formation. J. Biol. Chem. 282(1), 606–614 (2007). doi:10.1074/jbc.M606268200

    Article  PubMed  CAS  Google Scholar 

  68. Tran, D.T., Zhang, L., Zhang, Y., Tian, E., Earl, L.A., Ten Hagen, K.G.: Multiple members of the UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase family are essential for viability in Drosophila. J. Biol. Chem. 287(8), 5243–5252 (2012). doi:10.1074/jbc.M111.306159

    Article  PubMed  CAS  Google Scholar 

  69. Zhang, L., Zhang, Y., Hagen, K.G.: A mucin-type O-glycosyltransferase modulates cell adhesion during Drosophila development. J. Biol. Chem. 283(49), 34076–34086 (2008). doi:10.1074/jbc.M804267200

    Article  PubMed  CAS  Google Scholar 

  70. Fakhro, K.A., Choi, M., Ware, S.M., Belmont, J.W., Towbin, J.A., Lifton, R.P., Khokha, M.K., Brueckner, M.: Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning. Proc. Natl. Acad. Sci. U. S. A. 108(7), 2915–2920 (2011). doi:10.1073/pnas.1019645108

    Article  PubMed  Google Scholar 

  71. Guda, K., Moinova, H., He, J., Jamison, O., Ravi, L., Natale, L., Lutterbaugh, J., Lawrence, E., Lewis, S., Willson, J.K., Lowe, J.B., Wiesner, G.L., Parmigiani, G., Barnholtz-Sloan, J., Dawson, D.W., Velculescu, V.E., Kinzler, K.W., Papadopoulos, N., Vogelstein, B., Willis, J., Gerken, T.A., Markowitz, S.D.: Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers. Proc. Natl. Acad. Sci. U. S. A. 106(31), 12921–12925 (2009). doi:10.1073/pnas.0901454106

    Article  PubMed  Google Scholar 

  72. Ichikawa, S., Guigonis, V., Imel, E.A., Courouble, M., Heissat, S., Henley, J.D., Sorenson, A.H., Petit, B., Lienhardt, A., Econs, M.J.: Novel GALNT3 mutations causing hyperostosis-hyperphosphatemia syndrome result in low intact fibroblast growth factor 23 concentrations. J. Clin. Endocrinol. Metab. 92(5), 1943–1947 (2007). doi:10.1210/jc.2006-1825

    Article  PubMed  CAS  Google Scholar 

  73. Ju, T., Cummings, R.D.: Protein glycosylation: chaperone mutation in Tn syndrome. Nature 437(7063), 1252 (2005). doi:10.1038/4371252a

    Article  PubMed  CAS  Google Scholar 

  74. Kathiresan, S., Manning, A.K., Demissie, S., D'Agostino, R.B., Surti, A., Guiducci, C., Gianniny, L., Burtt, N.P., Melander, O., Orho-Melander, M., Arnett, D.K., Peloso, G.M., Ordovas, J.M., Cupples, L.A.: A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study. BMC Med. Genet. 8(Suppl 1), S17 (2007). doi:10.1186/1471-2350-8-S1-S17

    Article  PubMed  CAS  Google Scholar 

  75. Topaz, O., Shurman, D.L., Bergman, R., Indelman, M., Ratajczak, P., Mizrachi, M., Khamaysi, Z., Behar, D., Petronius, D., Friedman, V., Zelikovic, I., Raimer, S., Metzker, A., Richard, G., Sprecher, E.: Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. Nat. Genet. 36(6), 579–581 (2004). doi:10.1038/ng1358

    Article  PubMed  CAS  Google Scholar 

  76. Okajima, T., Reddy, B., Matsuda, T., Irvine, K.D.: Contributions of chaperone and glycosyltransferase activities of O-fucosyltransferase 1 to Notch signaling. BMC Biol. 6, 1 (2008). doi:10.1186/1741-7007-6-1

    Article  PubMed  CAS  Google Scholar 

  77. Sasamura, T., Ishikawa, H.O., Sasaki, N., Higashi, S., Kanai, M., Nakao, S., Ayukawa, T., Aigaki, T., Noda, K., Miyoshi, E., Taniguchi, N., Matsuno, K.: The O-fucosyltransferase O-fut1 is an extracellular component that is essential for the constitutive endocytic trafficking of Notch in Drosophila. Development 134(7), 1347–1356 (2007). doi:10.1242/dev.02811

    Article  PubMed  CAS  Google Scholar 

  78. Aoki, K., Porterfield, M., Lee, S.S., Dong, B., Nguyen, K., McGlamry, K.H., Tiemeyer, M.: The diversity of O-linked glycans expressed during Drosophila melanogaster development reflects stage- and tissue-specific requirements for cell signaling. J. Biol. Chem. 283(44), 30385–30400 (2008). doi:10.1074/jbc.M804925200

    Article  PubMed  CAS  Google Scholar 

  79. Ishikawa, H.O., Ayukawa, T., Nakayama, M., Higashi, S., Kamiyama, S., Nishihara, S., Aoki, K., Ishida, N., Sanai, Y., Matsuno, K.: 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(6), 4122–4129 (2010). doi:10.1074/jbc.M109.016964

    Article  PubMed  CAS  Google Scholar 

  80. Ishikawa, H.O., Higashi, S., Ayukawa, T., Sasamura, T., Kitagawa, M., Harigaya, K., Aoki, K., Ishida, N., Sanai, Y., Matsuno, K.: Notch deficiency implicated in the pathogenesis of congenital disorder of glycosylation IIc. Proc. Natl. Acad. Sci. U. S. A. 102(51), 18532–18537 (2005). doi:10.1073/pnas.0504115102

    Article  PubMed  CAS  Google Scholar 

  81. Yamakawa, T., Ayukawa, T., Matsuno, K.: Metabolism and transportation pathways of GDP-fucose that are required for the O-fucosylation of Notch. Adv. Exp. Med. Biol. 727, 37–46 (2012). doi:10.1007/978-1-4614-0899-4_3

    Article  PubMed  CAS  Google Scholar 

  82. Lubke, T., Marquardt, T., Etzioni, A., Hartmann, E., von Figura, K., Korner, C.: Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency. Nat. Genet. 28(1), 73–76 (2001). doi:10.1038/88299

    PubMed  CAS  Google Scholar 

  83. Luhn, K., Wild, M.K., Eckhardt, M., Gerardy-Schahn, R., Vestweber, D.: The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. Nat. Genet. 28(1), 69–72 (2001). doi:10.1038/88289

    PubMed  CAS  Google Scholar 

  84. Stanley, P., Okajima, T.: Roles of glycosylation in Notch signaling. Curr. Top. Dev. Biol. 92, 131–164 (2010). doi:10.1016/S0070-2153(10)92004-8

    Article  PubMed  CAS  Google Scholar 

  85. Acar, M., Jafar-Nejad, H., Takeuchi, H., Rajan, A., Ibrani, D., Rana, N.A., Pan, H., Haltiwanger, R.S., Bellen, H.J.: Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling. Cell 132(2), 247–258 (2008). doi:10.1016/j.cell.2007.12.016

    Article  PubMed  CAS  Google Scholar 

  86. Rana, N.A., Haltiwanger, R.S.: Fringe benefits: functional and structural impacts of O-glycosylation on the extracellular domain of Notch receptors. Curr. Opin. Struct. Biol. 21(5), 583–589 (2011). doi:10.1016/j.sbi.2011.08.008

    Article  PubMed  CAS  Google Scholar 

  87. Takeuchi, h., Fernandez-Valdivia, R.C., Caswell, D.S., Nita-Lazar, A., Rana, N.A., Garner, T.P., Weldeghioeghis, T.K., Macnaughtan, M.A., Jafar-Nejad, H., Haltiwanger, R.S.: Rumi functions as both a protein O-glucosyltransferase and a protein O-xylosyltransferase. Proceedings of the National Academy of Sciences of the United States of America (2011). doi:10.1073/pnas.1109696108/-/DCSupplemental

  88. Fernandez-Valdivia, R., Takeuchi, H., Samarghandi, A., Lopez, M., Leonardi, J., Haltiwanger, R.S., Jafar-Nejad, H.: Regulation of mammalian Notch signaling and embryonic development by the protein O-glucosyltransferase Rumi. Development 138(10), 1925–1934 (2011). doi:10.1242/dev.060020

    Article  PubMed  CAS  Google Scholar 

  89. Sethi, M.K., Buettner, F.F., Krylov, V.B., Takeuchi, H., Nifantiev, N.E., Haltiwanger, R.S., Gerardy-Schahn, R., Bakker, H.: Identification of glycosyltransferase 8 family members as xylosyltransferases acting on O-glucosylated notch epidermal growth factor repeats. J. Biol. Chem. 285(3), 1582–1586 (2010). doi:10.1074/jbc.C109.065409

    Article  PubMed  CAS  Google Scholar 

  90. Sethi, M.K., Buettner, F.F., Ashikov, A., Krylov, V.B., Takeuchi, H., Nifantiev, N.E., Haltiwanger, R.S., Gerardy-Schahn, R., Bakker, H.: Molecular cloning of a xylosyltransferase that transfers the second xylose to O-glucosylated epidermal growth factor repeats of notch. J. Biol. Chem. 287(4), 2739–2748 (2012). doi:10.1074/jbc.M111.302406

    Article  PubMed  CAS  Google Scholar 

  91. Matsuura, A., Ito, M., Sakaidani, Y., Kondo, T., Murakami, K., Furukawa, K., Nadano, D., Matsuda, T., Okajima, T.: O-linked N-acetylglucosamine is present on the extracellular domain of notch receptors. J. Biol. Chem. 283(51), 35486–35495 (2008). doi:10.1074/jbc.M806202200

    Article  PubMed  CAS  Google Scholar 

  92. Sakaidani, Y., Ichiyanagi, N., Saito, C., Nomura, T., Ito, M., Nishio, Y., Nadano, D., Matsuda, T., Furukawa, K., Okajima, T.: O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1. Biochem. Biophys. Res. Commun. 419(1), 14–19 (2012). doi:10.1016/j.bbrc.2012.01.098

    Article  PubMed  CAS  Google Scholar 

  93. Hart, G.W., Slawson, C., Ramirez-Correa, G., Lagerlof, O.: Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease. Annu. Rev. Biochem. 80, 825–858 (2011). doi:10.1146/annurev-biochem-060608-102511

    Article  PubMed  CAS  Google Scholar 

  94. Kreppel, L.K., Blomberg, M.A., Hart, G.W.: Dynamic glycosylation of nuclear and cytosolic proteins. Cloning and characterization of a unique O-GlcNAc transferase with multiple tetratricopeptide repeats. J. Biol. Chem. 272(14), 9308–9315 (1997)

    Article  PubMed  CAS  Google Scholar 

  95. Sakaidani, Y., Nomura, T., Matsuura, A., Ito, M., Suzuki, E., Murakami, K., Nadano, D., Matsuda, T., Furukawa, K., Okajima, T.: O-linked-N-acetylglucosamine on extracellular protein domains mediates epithelial cell-matrix interactions. Nat. Comm. 2, 583 (2011). doi:10.1038/ncomms1591

    Article  CAS  Google Scholar 

  96. Haines, N., Seabrooke, S., Stewart, B.A.: Dystroglycan and protein O-mannosyltransferases 1 and 2 are required to maintain integrity of Drosophila larval muscles. Mol. Biol. Cell 18(12), 4721–4730 (2007). doi:10.1091/mbc.E07-01-0047

    Article  PubMed  CAS  Google Scholar 

  97. Lyalin, D., Koles, K., Roosendaal, S.D., Repnikova, E., Van Wechel, L., Panin, V.M.: The twisted gene encodes Drosophila protein O-mannosyltransferase 2 and genetically interacts with the rotated abdomen gene encoding Drosophila protein O-mannosyltransferase 1. Genetics 172(1), 343–353 (2006). doi:10.1534/genetics.105.049650

    Article  PubMed  CAS  Google Scholar 

  98. Nakamura, N., Stalnaker, S.H., Lyalin, D., Lavrova, O., Wells, L., Panin, V.M.: Drosophila Dystroglycan is a target of O-mannosyltransferase activity of two protein O-mannosyltransferases. Rotated Abdomen and Twisted. Glycobiology 20(3), 381–394 (2010). doi:10.1093/glycob/cwp189

    Article  PubMed  CAS  Google Scholar 

  99. Barresi, R., Campbell, K.P.: Dystroglycan: from biosynthesis to pathogenesis of human disease. J. Cell Sci. 119(Pt 2), 199–207 (2006). doi:10.1242/jcs.02814

    Article  PubMed  CAS  Google Scholar 

  100. Yoshida-Moriguchi, T., Yu, L., Stalnaker, S.H., Davis, S., Kunz, S., Madson, M., Oldstone, M.B., Schachter, H., Wells, L., Campbell, K.P.: O-mannosyl phosphorylation of alpha-dystroglycan is required for laminin binding. Science 327(5961), 88–92 (2010). doi:10.1126/science.1180512

    Article  PubMed  CAS  Google Scholar 

  101. Dino, M.R., Harroch, S., Hockfield, S., Matthews, R.T.: Monoclonal antibody Cat-315 detects a glycoform of receptor protein tyrosine phosphatase beta/phosphacan early in CNS development that localizes to extrasynaptic sites prior to synapse formation. Neuroscience 142(4), 1055–1069 (2006). doi:10.1016/j.neuroscience.2006.07.054

    Article  PubMed  CAS  Google Scholar 

  102. Stalnaker, S.H., Aoki, K., Lim, J.M., Porterfield, M., Liu, M., Satz, J.S., Buskirk, S., Xiong, Y., Zhang, P., Campbell, K.P., Hu, H., Live, D., Tiemeyer, M., Wells, L.: Glycomic analyses of mouse models of congenital muscular dystrophy. J. Biol. Chem. 286(24), 21180–21190 (2011). doi:10.1074/jbc.M110.203281

    Article  PubMed  CAS  Google Scholar 

  103. Kozma, K., Keusch, J.J., Hegemann, B., Luther, K.B., Klein, D., Hess, D., Haltiwanger, R.S., Hofsteenge, J.: Identification and characterization of abeta1,3-glucosyltransferase that synthesizes the Glc-beta1,3-Fuc disaccharide on thrombospondin type 1 repeats. J. Biol. Chem. 281(48), 36742–36751 (2006). doi:10.1074/jbc.M605912200

    Article  PubMed  CAS  Google Scholar 

  104. Luo, Y., Koles, K., Vorndam, W., Haltiwanger, R.S., Panin, V.M.: Protein O-fucosyltransferase 2 adds O-fucose to thrombospondin type 1 repeats. J. Biol. Chem. 281(14), 9393–9399 (2006). doi:10.1074/jbc.M511975200

    Article  PubMed  CAS  Google Scholar 

  105. Hess, D., Keusch, J.J., Oberstein, S.A., Hennekam, R.C., Hofsteenge, J.: Peters Plus syndrome is a new congenital disorder of glycosylation and involves defective Omicron-glycosylation of thrombospondin type 1 repeats. J. Biol. Chem. 283(12), 7354–7360 (2008). doi:10.1074/jbc.M710251200

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the support of grant R01-GM072839 (to MT) from the National Institutes of Health/National Institute of General Medicine.

Author information

Authors and Affiliations

  1. The Complex Carbohydrate Research Center, University of Georgia, Athens, GA, 30602, USA

    Toshihiko Katoh & Michael Tiemeyer

  2. The Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, 30602, USA

    Michael Tiemeyer

Authors
  1. Toshihiko Katoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Tiemeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Tiemeyer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Katoh, T., Tiemeyer, M. The N’s and O’s of Drosophila glycoprotein glycobiology. Glycoconj J 30, 57–66 (2013). https://doi.org/10.1007/s10719-012-9442-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-012-9442-x

Keywords

Search

Navigation