Skip to main content
SpringerLink
Log in

Role of UDP-N-Acetylglucosamine2-Epimerase/N-Acetylmannosamine Kinase (GNE) in β1-Integrin-Mediated Cell Adhesion

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Hereditary inclusion body myopathy (GNE myopathy) is a neuromuscular disorder due to mutation in key sialic acid biosynthetic enzyme, GNE. The pathomechanism of the disease is poorly understood as GNE is involved in other cellular functions beside sialic acid synthesis. In the present study, a HEK293 cell-based model system has been established where GNE is either knocked down or over-expressed along with pathologically relevant GNE mutants (D176V and V572L). The subcellular distribution of recombinant GNE and its mutant showed differential localization in the cell. The effect of mutation on GNE function was investigated by studying hyposialylation of cell membrane receptor, β1-integrin. Hyposialylated β1-integrin localized to internal vesicles that was restored upon supplementation with sialic acid. Fibronectin stimulation caused migration of hyposialylated β1-integrin to the cell membrane and co-localization with focal adhesion kinase (FAK) leading to increased focal adhesion formation. This further activated FAK and Src, downstream signaling molecules and led to increased cell adhesion. This is the first report to show that mutation in GNE affects β1-integrin-mediated cell adhesion process in GNE mutant cells.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Edelman GM, Crossin KL (1991) Cell adhesion molecules: implications for a molecular histology. Annu Rev Biochem 60:155–190. doi:10.1146/annurev.bi.60.070191.001103

    Article  PubMed  CAS  Google Scholar 

  2. Severi E, Hood DW, Thomas GH (2007) Sialic acid utilization by bacterial pathogens. Microbiology 153(Pt 9):2817–2822. doi:10.1099/mic.0.2007/009480-0

    Article  PubMed  CAS  Google Scholar 

  3. Qian J, Zhu CH, Tang S, Shen AJ, Ai J, Li J, Geng MY, Ding J (2009) Alpha2,6-hyposialylation of c-Met abolishes cell motility of ST6Gal-I-knockdown HCT116 cells. Acta Pharmacol Sin 30(7):1039–1045. doi:10.1038/aps.2009.84

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Frenzel R, Krohn K, Eszlinger M, Tonjes A, Paschke R (2005) Sialylation of human thyrotropin receptor improves and prolongs its cell-surface expression. Mol Pharmacol 68(4):1106–1113. doi:10.1124/mol.105.012906

    Article  PubMed  CAS  Google Scholar 

  5. Kitazume S, Imamaki R, Ogawa K, Komi Y, Futakawa S, Kojima S, Hashimoto Y, Marth JD, Paulson JC, Taniguchi N (2010) Alpha2,6-sialic acid on platelet endothelial cell adhesion molecule (PECAM) regulates its homophilic interactions and downstream antiapoptotic signalling. J Biol Chem 285(9):6515–6521. doi:10.1074/jbc.M109.073106

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Bennett E, Urcan MS, Tinkle SS, Koszowski AG, Levinson SR (1997) Contribution of sialic acid to the voltage dependence of sodium channel gating—a possible electrostatic mechanism. J Gen Physiol 109(3):327–343. doi:10.1085/jgp.109.3.327

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Bi S, Baum LG (2009) Sialic acids in T cell development and function. Biochem Biophys Acta 1790(12):1599–1610. doi:10.1016/j.bbagen.2009.07.027

    Article  PubMed  CAS  Google Scholar 

  8. Narayanan S (1994) Sialic-acid as a tumor-marker. Ann Clin Lab Sci 24(4):376–384

    PubMed  CAS  Google Scholar 

  9. Stasche R, Hinderlich S, Weise C, Effertz K, Lucka L, Moormann P, Reutter W (1997) A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver—molecular cloning and functional expression of UDP-N-acetyl-glucosamine 2-epimerase/N-acetylmannosamine kinase. J Biol Chem 272(39):24319–24324. doi:10.1074/jbc.272.39.24319

    Article  PubMed  CAS  Google Scholar 

  10. Ghaderi D, Strauss HM, Reinke S, Cirak S, Reutter W, Lucka L, Hinderlich S (2007) Evidence for dynamic interplay of different oligomeric states of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase by biophysical methods. J Mol Biol 369(3):746–758. doi:10.1016/j.jmb.2007.03.037

    Article  PubMed  CAS  Google Scholar 

  11. Villavicencio-Lorini P, Laabs S, Danker K, Reutter W, Horstkorte R (2002) Biochemical engineering of the acyl side chain of sialic acids stimulates integrin-dependent adhesion of HL60 cells to fibronectin. J Mol Med-Jmm 80(10):671–677. doi:10.1007/s00109-002-0382-y

    Article  CAS  Google Scholar 

  12. Seppala R, Lehto VP, Gahl WA (1999) Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme. Am J Hum Genet 64(6):1563–1569. doi:10.1086/302411

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Hinderlich S, Stasche R, Zeitler R, Reutter W (1997) A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver. Purification and characterization of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. J Biol Chem 272(39):24313–24318. doi:10.1074/jbc.272.39.24313

    Article  PubMed  CAS  Google Scholar 

  14. Noguchi S, Keira Y, Murayama K, Ogawa M, Fujita M, Kawahara G, Oya Y, Imazawa M, Goto Y, Hayashi YK, Nonaka I, Nishino I (2004) Reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase activity and sialylation in distal myopathy with rimmed vacuoles. J Biol Chem 279(12):11402–11407. doi:10.1074/jbc.M313171200

    Article  PubMed  CAS  Google Scholar 

  15. Krause S, Hinderlich S, Amsili S, Horstkorte R, Wiendl H, Argov Z, Mitrani-Rosenbaum S, Lochmuller H (2005) Localization of UDP-GlcNAc 2-epimerase/ManAc kinase (GNE) in the Golgi complex and the nucleus of mammalian cells. Exp Cell Res 304(2):365–379. doi:10.1016/j.yexcr.2004.11.010

    Article  PubMed  CAS  Google Scholar 

  16. Weidemann W, Stelzl U, Lisewski U, Bork K, Wanker EE, Hinderlich S, Horstkorte R (2006) The collapsin response mediator protein 1 (CRMP-1) and the promyelocytic leukemia zinc finger protein (PLZF) bind to UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), the key enzyme of sialic acid biosynthesis. FEBS Lett 580(28–29):6649–6654. doi:10.1016/j.febslet.2006.11.015

    Article  PubMed  CAS  Google Scholar 

  17. Amsili S, Zer H, Hinderlich S, Krause S, Becker-Cohen M, MacArthur DG, North KN, Mitrani-Rosenbaum S (2008) UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) binds to alpha-actinin 1: novel pathways in skeletal muscle? Plos One 3(6):e2477. doi:10.1371/journal.pone.0002477

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wang Z, Sun Z, Li AV, Yarema KJ (2006) Roles for UDP-GlcNAc 2-epimerase/ManNAc 6-kinase outside of sialic acid biosynthesis: modulation of sialyltransferase and BiP expression, GM3 and GD3 biosynthesis, proliferation, and apoptosis, and ERK1/2 phosphorylation. J Biol Chem 281(37):27016–27028. doi:10.1074/jbc.M604903200

    Article  PubMed  CAS  Google Scholar 

  19. Eisenberg I, Avidan N, Potikha T, Hochner H, Chen M, Olender T, Barash M, Shemesh M, Sadeh M, Grabov-Nardini G, Shmilevich I, Friedmann A, Karpati G, Bradley WG, Baumbach L, Lancet D, Ben Asher E, Beckmann JS, Argov Z, Mitrani-Rosenbaum S (2001) The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy. Nat Genet 29(1):83–87. doi:10.1038/ng718

    Article  PubMed  CAS  Google Scholar 

  20. Seppala R, Tietze F, Krasnewich D, Weiss P, Ashwell G, Barsh G, Thomas GH, Packman S, Gahl WA (1991) Sialic acid metabolism in sialuria fibroblasts. J Biol Chem 266(12):7456–7461

    PubMed  CAS  Google Scholar 

  21. Tasca G, Ricci E, Monforte M, Laschena F, Ottaviani P, Rodolico C, Barca E, Silvestri G, Iannaccone E, Mirabella M, Broccolini A (2012) Muscle imaging findings in GNE myopathy. J Neurol 259(7):1358–1365. doi:10.1007/s00415-011-6357-6

    Article  PubMed  Google Scholar 

  22. Yoshimura M, Monma K, Suzuki N, Aoki M, Kumamoto T, Tanaka K, Tomimitsu H, Nakano S, Sonoo M, Shimizu J, Sugie K, Nakamura H, Oya Y, Hayashi YK, Malicdan MC, Noguchi S, Murata M, Nishino I (2012) Heterozygous UDP-GlcNAc 2-epimerase and N-acetylmannosamine kinase domain mutations in the GNE gene result in a less severe GNE myopathy phenotype compared to homozygous N-acetylmannosamine kinase domain mutations. J Neurol Sci 318(1–2):100–105. doi:10.1016/j.jns.2012.03.016

    Article  Google Scholar 

  23. Argov Z, Eisenberg I, Grabov-Nardini G, Sadeh M, Wirguin I, Soffer D, Mitrani-Rosenbaum S (2003) Hereditary inclusion body myopathy: the Middle Eastern genetic cluster. Neurology 60(9):1519–1523

    Article  PubMed  CAS  Google Scholar 

  24. Park YE, Kim HS, Choi ES, Shin JH, Kim SY, Son EH, Lee CH, Kim DS (2012) Limb-girdle phenotype is frequent in patients with myopathy associated with GNE mutations. J Neurol Sci 321(1–2):77–81. doi:10.1016/j.jns.2012.07.061

    Article  PubMed  CAS  Google Scholar 

  25. Schwarzkopf M, Knobeloch KP, Rohde E, Hinderlich S, Wiechens N, Lucka L, Horak I, Reutter W, Horstkorte R (2002) Sialylation is essential for early development in mice. Proc Natl Acad Sci U S A 99(8):5267–5270. doi:http://www.ncbi.nlm.nih.gov/pubmed/11929971

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Malicdan MC, Noguchi S, Nonaka I, Hayashi YK, Nishino I (2007) A Gne knockout mouse expressing human GNE D176V mutation develops features similar to distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy. Hum Mol Genet 16(22):2669–2682. doi:10.1093/hmg/ddm220

    Article  PubMed  CAS  Google Scholar 

  27. Ito M, Sugihara K, Asaka T, Toyama T, Yoshihara T, Furuichi K, Wada T, Asano M (2012) Glycoprotein hyposialylation gives rise to a nephrotic-like syndrome that is prevented by sialic acid administration in GNE V572L point-mutant mice. PLoS One 7(1):e29873. doi:10.1371/journal.pone.0029873

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Sela I, Milman Krentsis I, Shlomai Z, Sadeh M, Dabby R, Argov Z, Ben-Bassat H, Mitrani-Rosenbaum S (2011) The proteomic profile of hereditary inclusion body myopathy. PLoS One 6(1):e16334. doi:10.1371/journal.pone.0016334

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Carson JA, Wei L (2000) Integrin signalling’s potential for mediating gene expression in hypertrophying skeletal muscle. J Appl Physiol 88(1):337–343

    PubMed  CAS  Google Scholar 

  30. Perkins AD, Ellis SJ, Asghari P, Shamsian A, Moore ED, Tanentzapf G (2010) Integrin-mediated adhesion maintains sarcomeric integrity. Dev Biol 338(1):15–27. doi:10.1016/j.ydbio.2009.10.034

    Article  PubMed  CAS  Google Scholar 

  31. Semel AC, Seales EC, Singhal A, Eklund EA, Colley KJ, Bellis SL (2002) Hyposialylation of integrins stimulates the activity of myeloid fibronectin receptors. J Biol Chem 277(36):32830–32836. doi:10.1074/jbc.M202493200

    Article  PubMed  CAS  Google Scholar 

  32. Ricci E, Broccolini A, Gidaro T, Morosetti R, Gliubizzi C, Frusciante R, Di Lella GM, Tonali PA, Mirabella M (2006) NCAM is hyposialylated in hereditary inclusion body myopathy due to GNE mutations. Neurology 66(5):755–758

    Article  PubMed  CAS  Google Scholar 

  33. Huizing M, Rakocevic G, Sparks SE, Mamali L, Shatunov A, Goldfarb L, Krasnewich D, Gahl WA, Dalakas MC (2004) Hypoglycosylation of alpha-dystroglycan in patients with hereditary IBM due to GNE mutations. Mol Genet Metab 81(3):196–202. doi:10.1016/j.ymgme.2003.11.012

    Article  PubMed  CAS  Google Scholar 

  34. Gagiannis D, Orthmann A, Danssmann I, Schwarzkopf M, Weidemann W, Horstkorte R (2007) Reduced sialylation status in UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE)-deficient mice. Glycoconjugate J 24(2–3):125–130. doi:10.1007/s10719-006-9019-7

    Article  CAS  Google Scholar 

  35. Broccolini A, Gidaro T, De Cristofaro R, Morosetti R, Gliubizzi C, Ricci E, Tonali PA, Mirabella M (2008) Hyposialylation of neprilysin possibly affects its expression and enzymatic activity in hereditary inclusion-body myopathy muscle. J Neurochem 105(3):971–981. doi:10.1111/j.1471-4159.2007.05208.x

    Article  PubMed  CAS  Google Scholar 

  36. Pretzlaff RK, Xue VW, Rowin ME (2000) Sialidase treatment exposes the beta1-integrin active ligand binding site on HL60 cells and increases binding to fibronectin. Cell Adhes Commun 7(6):491–500

    Article  PubMed  CAS  Google Scholar 

  37. Penner J, Mantey LR, Elgavish S, Ghaderi D, Cirak S, Berger M, Krause S, Lucka L, Voit T, Mitrani-Rosenbaum S, Hinderlich S (2006) Influence of UDP-GlcNAc 2-epimerase/ManNAc kinase mutant proteins on hereditary inclusion body myopathy. Biochemistry 45(9):2968–2977. doi:10.1021/bi0522504

    Article  PubMed  CAS  Google Scholar 

  38. Sparks SE, Ciccone C, Lalor M, Orvisky E, Klootwijk R, Savelkoul PJ, Dalakas MC, Krasnewich DM, Gahl WA, Huizing M (2005) Use of a cell-free system to determine UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities in human hereditary inclusion body myopathy. Glycobiology 15(11):1102–1110. doi:10.1093/glycob/cwi100

    Article  PubMed  CAS  Google Scholar 

  39. Effertz K, Hinderlich S, Reutter W (1999) Selective loss of either the epimerase or kinase activity of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase due to site-directed mutagenesis based on sequence alignments. J Biol Chem 274(40):28771–28778. doi:10.1074/jbc.274.40.28771

    Article  PubMed  CAS  Google Scholar 

  40. Blume A, Ghaderi D, Liebich V, Hinderlich S, Donner P, Reutter W, Lucka L (2004) UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, functionally expressed in and purified from Escherichia coli, yeast, and insect cells. Protein Expres Purif 35(2):387–396. doi:10.1016/j.pep.2004.02.013

    Article  CAS  Google Scholar 

  41. Harburger DS, Calderwood DA (2009) Integrin signalling at a glance. J Cell Sci 122(2):159–163. doi:10.1242/Jcs.018093

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  42. Shi Q, Boettiger D (2003) A novel mode for integrin-mediated signaling: tethering is required for phosphorylation of FAK Y397. Mol Biol Cell 14(10):4306–4315. doi:10.1091/mbc.E03-01-0046

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  43. Malicdan MCV, Noguchi S, Hayashi YK, Nonaka I, Nishino I (2009) Prophylactic treatment with sialic acid metabolites precludes the development of the myopathic phenotype in the DMRV-hIBM mouse model. Nat Med 15(6):690–U127. doi:10.1038/Nm.1956

    Article  PubMed  CAS  Google Scholar 

  44. Tomimitsu H, Ishikawa K, Shimizu J, Ohkoshi N, Kanazawa I, Mizusawa H (2002) Distal myopathy with rimmed vacuoles: novel mutations in the GNE gene. Neurology 59(3):451–454

    Article  PubMed  CAS  Google Scholar 

  45. Saito F, Tomimitsu H, Arai K, Nakai S, Kanda T, Shimizu T, Mizusawa H, Matsumura K (2004) A Japanese patient with distal myopathy with rimmed vacuoles: missense mutations in the epimerase domain of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene accompanied by hyposialylation of skeletal muscle glycoproteins. Neuromuscul Disord 14(2):158–161. doi:10.1016/j.nmd.2003.09.006

    Article  PubMed  CAS  Google Scholar 

  46. Salama I, Hinderlich S, Shlomai Z, Eisenberg I, Krause S, Yarema K, Argov Z, Lochmuller H, Reutter W, Dabby R, Sadeh M, Ben-Bassat H, Mitrani-Rosenbaum S (2005) No overall hyposialylation in hereditary inclusion body myopathy myoblasts carrying the homozygous M712T GNE mutation. Biochem Bioph Res Co 328(1):221–226. doi:10.1016/j.bbrc.2004.12.157

    Article  CAS  Google Scholar 

  47. Keppler OT, Hinderlich S, Langner J, Schwartz-Albiez R, Reutter W, Pawlita M (1999) UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation. Science 284(5418):1372–1376

    Article  PubMed  CAS  Google Scholar 

  48. Argov Z, Mitrani-Rosenbaum S (2008) The hereditary inclusion body myopathy enigma and its future therapy. Neurotherapeutics 5(4):633–637. doi:10.1016/j.nurt.2008.07.004

    Article  PubMed  CAS  Google Scholar 

  49. Li HH, Chen Q, Liu FC, Zhang XM, Li W, Liu SP, Zhao YY, Gong YQ, Yan CZ (2013) Unfolded protein response and activated degradative pathways regulation in GNE myopathy. PLoS One 8 (3). doi:10.1371/journal.pone.0058116

  50. Bendas G, Borsig L (2012) Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins. Int J Cell Biol 2012:676731. doi:10.1155/2012/676731

    Article  PubMed  PubMed Central  Google Scholar 

  51. Hynes RO, Yamada KM (1982) Fibronectins: multifunctional modular glycoproteins. J Cell Biol 95(2 Pt 1):369–377

    Article  PubMed  CAS  Google Scholar 

  52. Pan D, Song Y (2010) Role of altered sialylation of the I-like domain of beta1 integrin in the binding of fibronectin to beta1 integrin: thermodynamics and conformational analyses. Biophys J 99(1):208–217. doi:10.1016/j.bpj.2010.03.063

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  53. Seales EC, Shaikh FM, Woodard-Grice AV, Aggarwal P, McBrayer AC, Hennessy KM, Bellis SL (2005) A protein kinase C/Ras/ERK signaling pathway activates myeloid fibronectin receptors by altering beta1 integrin sialylation. J Biol Chem 280(45):37610–37615. doi:10.1074/jbc.M508476200

    Article  PubMed  CAS  Google Scholar 

  54. Disatnik MH, Boutet SC, Lee CH, Mochly-Rosen D, Rando TA (2002) Sequential activation of individual PKC isozymes in integrin-mediated muscle cell spreading: a role for MARCKS in an integrin signaling pathway. J Cell Sci 115(Pt 10):2151–2163

    PubMed  CAS  Google Scholar 

  55. Lowin T, Straub RH, Neumann E, Bosserhoff A, Vogel C, Moissl C, Anders S, Muller-Ladner U, Schedel J (2009) Glucocorticoids increase alpha 5 integrin expression and adhesion of synovial fibroblasts but inhibit ERK signaling, migration, and cartilage invasion. Arthritis Rheum 60(12):3623–3632. doi:10.1002/Art.24985

    Article  PubMed  CAS  Google Scholar 

  56. Sinanan ACM, Machell JRA, Wynne-Hughes GT, Hunt NP, Lewis MR (2008) Alpha v beta 3 and alpha v beta 5 integrins and their role in muscle precursor cell adhesion. Biol Cell 100(8):465–477. doi:10.1042/Bc20070115

    Article  PubMed  CAS  Google Scholar 

  57. Mayer U (2003) Integrins: redundant or important players in skeletal muscle? J Biol Chem 278(17):14587–14590. doi:10.1074/jbc.R200022200

    Article  PubMed  CAS  Google Scholar 

  58. Galeano B, Klootwijk R, Manoli I, Sun M, Ciccone C, Darvish D, Starost MF, Zerfas PM, Hoffmann VJ, Hoogstraten-Miller S, Krasnewich DM, Gahl WA, Huizing M (2007) Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N-acetylmannosamine. J Clin Invest 117(6):1585–1594. doi:10.1172/Jci30954

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  59. Takeda T, McQuistan T, Orlando RA, Farquhar MG (2001) Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton. J Clin Invest 108(2):289–301. doi:10.1172/Jci12539

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  60. Arya R, Kedar V, Hwang JR, McDonough H, Li HH, Taylor J, Patterson C (2004) Muscle ring finger protein-1 inhibits PKC epsilon activation and prevents cardiomyocyte hypertrophy. J Cell Biol 167(6):1147–1159. doi:10.1083/jcb.200402033

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  61. William E, Balch WGD, Braell WA, Rothman JE (1984) Reconstitution of the transport of protein between successive compartments of the golgi measured by the coupled incorporation of N-acetylglucosamine. Cell 39:405–416

    Article  Google Scholar 

  62. Homer KA, Roberts G, Byers HL, Tarelli E, Whiley RA, Philpott-Howard J, Beighton D (2001) Mannosidase production by viridans group streptococci. J Clin Microbiol 39(3):995–1001. doi:10.1128/JCM.39.3.995-1001.2001

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  63. Blume A, Chen H, Reutter W, Schmidt RR, Hinderlich S (2002) 2′,3′-Dialdehydo-UDP-N-acetylglucosamine inhibits UDP-N-acetylglucosamine 2-epimerase, the key enzyme of sialic acid biosynthesis. Febs Lett 521(1–3):127–132. doi:10.1016/S0014-5793(02)02856-9

    Article  PubMed  CAS  Google Scholar 

  64. Reissig JL, Storminger JL, Leloir LF (1955) A modified colorimetric method for the estimation of N-acetylamino sugars. J Biol Chem 217(2):959–966

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Prof. Alok Bhattacharya (School of Life Sciences, Jawaharlal Nehru University, New Delhi) for valuable discussions and helpful comments during the project. This research was supported by grants from DST Fast Track and Council of Scientific and Industrial Research, Govt. of India. We acknowledge Advanced Instrument Research Facility, Jawaharlal Nehru University, New Delhi for technical assistance in confocal microscopy and live cell imaging.

Author information

Authors and Affiliations

  1. School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India

    Sonam Grover & Ranjana Arya

Authors
  1. Sonam Grover
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ranjana Arya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ranjana Arya.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grover, S., Arya, R. Role of UDP-N-Acetylglucosamine2-Epimerase/N-Acetylmannosamine Kinase (GNE) in β1-Integrin-Mediated Cell Adhesion. Mol Neurobiol 50, 257–273 (2014). https://doi.org/10.1007/s12035-013-8604-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-013-8604-6

Keywords

Search

Navigation