Skip to main content
Log in

Where catabolism meets signalling: neuraminidase 1 as a modulator of cell receptors

  • Review
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Terminal sialic acid residues are found in abundance in glycan chains of glycoproteins and glycolipids on the surface of all live cells forming an outer layer of the cell originally known as glycocalyx. Their presence affects the molecular properties and structure of glycoconjugates, modifying their function and interactions with other molecules. Consequently, the sialylation state of glycoproteins and glycolipids has been recognized as a critical factor modulating molecular recognitions inside the cell, between the cells, between the cells and the extracellular matrix, and between the cells and certain exogenous pathogens. Sialyltransferases that attach sialic acid residues to the glycan chains in the process of their initial synthesis were thought to be mainly responsible for the creation and maintenance of a temporal and spatial diversity of sialylated moieties. However, the growing evidence also suggests that in mammalian cells, at least equally important roles belong to sialidases/neuraminidases, which are located on the cell surface and in intracellular compartments, and may either initiate the catabolism of sialoglycoconjugates or just cleave their sialic acid residues, and thereby contribute to temporal changes in their structure and functions. The current review summarizes emerging data demonstrating that neuraminidase 1 (NEU1), well known for its lysosomal catabolic function, can be also targeted to the cell surface and assume the previously unrecognized role as a structural and functional modulator of cellular receptors.

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

Access this article

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

Abbreviations

4MU-NeuAc:

(2′-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid

CathA:

cathepsin A/protective protein

ddNeuAc:

2,3-dehydro-2-deoxy-N-acetylneuraminic acid

EBP:

elastin-binding protein

FcγR:

Fc receptors for immunoglobulin G

GAL:

β-galactosidase

GS:

galactosialidosis

IGF-II:

insulin-like growth factor II

IL-4:

interleukin 4

IFN:

interferon

IR:

insulin receptor

LAMP-1:

lysosome associated membrane protein 1

LPS:

lipopolysaccharide

LSD:

lysosomal storage disease

NEU1:

neuraminidase 1

NEU2:

neuraminidase 2

NEU3:

neuraminidase 3

NEU4:

neuraminidase 4

PDGF:

platelet-derived growth factor

SGC:

sialoglycoconjugate

Sia:

sialic acid

SMC:

smooth muscle cells

Syk:

serine-tyrosine kinase

TLR:

Toll-like receptor

References

  1. Cohen, M., Varki, A.: The sialome–far more than the sum of its parts. OMICS 14, 455–464 (2010)

    Article  PubMed  CAS  Google Scholar 

  2. Kundra, R., Kornfeld, S.: Asparagine-linked oligosaccharides protect Lamp-1 and Lamp-2 from intracellular proteolysis. J. Biol. Chem. 274, 31039–31046 (1999)

    Article  PubMed  CAS  Google Scholar 

  3. Varki, A., Angata, T.: Siglecs–the major subfamily of I-type lectins. Glycobiology 16, 1R–27R (2006)

    Article  PubMed  CAS  Google Scholar 

  4. Cohen, M., Hurtado-Ziola, N., Varki, A.: ABO blood group glycans modulate sialic acid recognition on erythrocytes. Blood 114, 3668–3676 (2009)

    Article  PubMed  CAS  Google Scholar 

  5. Hakomori, S.: Structure, organization, and function of glycosphingolipids in membrane. Curr. Opin. Hematol. 10, 16–24 (2003)

    Article  PubMed  CAS  Google Scholar 

  6. Hakomori, S.: Carbohydrate-to-carbohydrate interaction, through glycosynapse, as a basis of cell recognition and membrane organization. Glycoconj. J. 21, 125–137 (2004)

    Article  PubMed  CAS  Google Scholar 

  7. Todeschini, A.R., Hakomori, S.I.: Functional role of glycosphingolipids and gangliosides in control of cell adhesion, motility, and growth, through glycosynaptic microdomains. Biochim. Biophys. Acta 1780, 421–433 (2008)

    Google Scholar 

  8. Jones, C.J., Aplin, J.D., Mulholland, J., Glasser, S.R.: Patterns of sialylation in differentiating rat decidual cells as revealed by lectin histochemistry. J. Reprod. Fertil. 99, 635–645 (1993)

    Article  PubMed  CAS  Google Scholar 

  9. Kelm, S., Schauer, R.: Sialic acids in molecular and cellular interactions. Int. Rev. Cytol. 175, 137–240 (1997)

    Article  PubMed  CAS  Google Scholar 

  10. Lehmann, F., Tiralongo, E., Tiralongo, J.: Sialic acid-specific lectins: occurrence, specificity and function. Cell. Mol. Life Sci. 63, 1331–1354 (2006)

    Article  PubMed  CAS  Google Scholar 

  11. Allende, M.L., Proia, R.L.: Lubricating cell signaling pathways with gangliosides. Curr. Opin. Struct. Biol. 12, 587–592 (2002)

    Article  PubMed  CAS  Google Scholar 

  12. Takashima, S.: Characterization of mouse sialyltransferase genes: their evolution and diversity. Biosci. Biotechnol. Biochem. 72, 1155–1167 (2008)

    Article  PubMed  CAS  Google Scholar 

  13. Kreisel, W., Volk, B.A., Büchsel, R., Reutter, W.: Different half-lives of the carbohydrate and protein moieties of a 110,000-dalton glycoprotein isolated from plasma membranes of rat liver. Proc. Natl. Acad. Sci. U.S.A. 77, 1828–1831 (1980)

    Article  PubMed  CAS  Google Scholar 

  14. Tauber, R., Park, C.S., Reutter, W.: Intramolecular heterogeneity of degradation in plasma membrane glycoproteins: evidence for a general characteristic. Proc. Natl. Acad. Sci. U.S.A. 80, 4026–4029 (1983)

    Article  PubMed  CAS  Google Scholar 

  15. Kopitz, J., von Reitzenstein, C., Sinz, K., Cantz, M.: Selective ganglioside desialylation in the plasma membrane of human neuroblastoma cells. Glycobiology 6, 367–376 (1996)

    Article  PubMed  CAS  Google Scholar 

  16. Kreisel, W., Hanski, C., Tran-Thi, T.A., Katz, N., Decker, K., Reutter, W., Gerok, W.: Remodeling of a rat hepatocyte plasma membrane glycoprotein. De-and reglycosylation of dipeptidyl peptidase IV. J. Biol. Chem. 263, 11736–11742 (1988)

    PubMed  CAS  Google Scholar 

  17. Monti, E., Preti, A., Venerando, B., Borsani, G.: Recent development in mammalian sialidase molecular biology. Neurochem. Res. 27, 649–663 (2002)

    Article  PubMed  CAS  Google Scholar 

  18. Saito, N., Yu, R.K.: Biochemistry and function of sialidases. In: Rosenberg, A. (ed.) Biology of sialic acids, pp. 261–313. Plenum Press, New York (1995)

    Google Scholar 

  19. Bonten, E., van der Spoel, A., Fornerod, M., Grosveld, G., D’Azzo, A.: Characterization of human lysosomal neuraminidase defines the molecular basis of the metabolic storage disorder sialidosis. Genes. Dev. 10, 3156–3169 (1996)

    Article  PubMed  CAS  Google Scholar 

  20. Milner, C.M., Smith, S.V., Carrillo, M.B., Taylor, G.L., Hollinshead, M., Campbell, R.D.: Identification of a sialidase encoded in the human major histocompatibility complex. J. Biol. Chem. 272, 4549–4558 (1997)

    Article  PubMed  CAS  Google Scholar 

  21. Pshezhetsky, A.V., Richard, C., Michaud, L., Igdoura, S., Wang, S., Elsliger, M.A., Qu, J., Leclerc, D., Gravel, R., Dallaire, L., Potier, M.: Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis. Nat. Genet. 15, 316–320 (1997)

    Article  PubMed  CAS  Google Scholar 

  22. Miyagi, T., Konno, K., Emori, Y., Kawasaki, H., Suzuki, K., Yasui, A., Tsuik, S.: Molecular cloning and expression of cDNA encoding rat skeletal muscle cytosolic sialidase. J. Biol. Chem. 268, 26435–26440 (1993)

    PubMed  CAS  Google Scholar 

  23. Monti, E., Preti, A., Rossi, E., Ballabio, A., Borsani, G.: Cloning and characterization of NEU2, a human gene homologous to rodent soluble sialidases. Genomics 57, 137–143 (1999)

    Article  PubMed  CAS  Google Scholar 

  24. Miyagi, T., Wada, T., Iwamatsu, A., Hata, K., Yoshikawa, Y., Tokuyama, S., Sawada, M.: Molecular cloning and characterization of a plasma membrane-associated sialidase specific for gangliosides. J. Biol. Chem. 274, 5004–5011 (1999)

    Article  PubMed  CAS  Google Scholar 

  25. Wada, T., Yoshikawa, Y., Tokuyama, S., Kuwabara, M., Akita, H., Miyagi, T.: Cloning, expression, and chromosomal mapping of a human ganglioside sialidase. Biochem. Biophys. Res. Commun. 261, 21–27 (1999)

    Article  PubMed  CAS  Google Scholar 

  26. Monti, E., Bassi, M.T., Papini, N., Riboni, M., Manzoni, M., Venerando, B., Croci, G., Preti, A., Ballabio, A., Tettamanti, G., Borsani, G.: Identification and expression of NEU3, a novel human sialidase associated to the plasma membrane. Biochem. J. 349, 343–351 (2000)

    Article  PubMed  CAS  Google Scholar 

  27. Comelli, E.M., Amado, M., Lustig, S.R., Paulson, J.C.: Identification and expression of Neu4, a novel murine sialidase. Gene 321, 155–161 (2003)

    Article  PubMed  CAS  Google Scholar 

  28. Monti, E., Bassi, M.T., Bresciani, R., Civini, S., Croci, G.L., Papini, N., Riboni, M., Zanchetti, G., Ballabio, A., Preti, A., Tettamanti, G., Venerando, B., Borsani, G.: Molecular cloning and characterization of NEU4, the fourth member of the human sialidase gene family. Genomics 83, 445–453 (2004)

    Article  PubMed  CAS  Google Scholar 

  29. Seyrantepe, V., Landry, K., Trudel, S., Hassan, J.A., Morales, C.R., Pshezhetsky, A.V.: Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells. J. Biol. Chem. 279, 37021–37029 (2004)

    Article  PubMed  CAS  Google Scholar 

  30. Miyagi, T., Tsuiki, S.: Purification and characterization of cytosolic sialidase from rat liver. J. Biol. Chem. 260, 6710–6716 (1985)

    PubMed  CAS  Google Scholar 

  31. Tringali, C., Papini, N., Fusi, P., Croci, G., Borsani, G., Preti, A., Tortora, P., Tettamanti, G., Venerando, B., Monti, E.: Properties of recombinant human cytosolic sialidase HsNEU2. The enzyme hydrolyzes monomerically dispersed GM1 ganglioside molecules. J. Biol. Chem. 279, 3169–1379 (2004)

    Article  PubMed  CAS  Google Scholar 

  32. Wang, Y., Yamaguchi, K., Wada, T., Hata, K., Zhao, X., Fujimoto, T., Miyagi, T.: A close association of the ganglioside-specific sialidase Neu3 with caveolin in membrane microdomains. J. Biol. Chem. 277, 26252–26259 (2002)

    Article  PubMed  CAS  Google Scholar 

  33. Zanchetti, G., Colombi, P., Manzoni, M., Anastasia, L., Caimi, L., Borsani, G., Venerando, B., Tettamanti, G., Preti, A., Monti, E., Bresciani, R.: Sialidase NEU3 is a peripheral membrane protein localized on the cell surface and in endosomal structures. Biochem. J. 408, 211–219 (2007)

    Article  PubMed  CAS  Google Scholar 

  34. Yamaguchi, K., Hata, K., Koseki, K., Shiozaki, K., Akita, H., Wada, T., Moriya, S., Miyagi, T.: Evidence for mitochondrial localization of a novel human sialidase (NEU4). Biochem. J. 390, 85–93 (2005)

    Article  PubMed  CAS  Google Scholar 

  35. Bigi, A., Morosi, L., Pozzi, C., Forcella, M., Tettamanti, G., Venerando, B., Monti, E., Fusi, P.: Human sialidase NEU4 long and short are extrinsic proteins bound to outer mitochondrial membrane and the endoplasmic reticulum, respectively. Glycobiology 20, 148–157 (2010)

    Article  PubMed  CAS  Google Scholar 

  36. Monti, E., Bonten, E., D’Azzo, A., Bresciani, R., Venerando, B., Borsani, G., Schauer, R., Tettamanti, G.: Sialidases in vertebrates: a family of enzymes tailored for several cell functions. Adv. Carbohydr. Chem. Biochem. 64, 403–479 (2010)

    Article  PubMed  CAS  Google Scholar 

  37. Miyagi, T.: Aberrant expression of sialidase and cancer progression. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 84, 407–418 (2008)

    Article  PubMed  CAS  Google Scholar 

  38. Oohira, T., Nagata, N., Akaboshi, I., Matsuda, I., Naito, S.: The infantile form of SL type II associated with congenital adrenal hyperplasia: possible linkage between HLA and the neuraminidase deficiency gene. Hum. Genet. 70, 341–343 (1985)

    Article  PubMed  CAS  Google Scholar 

  39. Pshezhetsky, A.V., Ashmarina, M.: Lysosomal multienzyme complex: biochemistry, genetics, and molecular pathophysiology. Prog. Nucleic Acid Res. Mol. Biol. 69, 81–114 (2001)

    Article  PubMed  CAS  Google Scholar 

  40. Lukong, K.E., Seyrantepe, V., Landry, K., Trudel, S., Ahmad, A., Gahl, W.A., Lefrancois, S., Morales, C.R., Pshezhetsky, A.V.: J. Biol. Chem. 276, 46172–46181 (2001)

    Article  PubMed  CAS  Google Scholar 

  41. Vinogradova, M.V., Michaud, L., Mezentsev, A.V., Lukong, K.E., El-Alfy, M., Morales, C.R., Potier, M., Pshezhetsky, A.V.: Molecular mechanism of lysosomal sialidase deficiency in galactosialidosis involves its rapid degradation. Biochem. J. 330, 641–650 (1998)

    PubMed  CAS  Google Scholar 

  42. Cross, A.S., Wright, D.G.: Mobilization of sialidase from intracellular stores to the surface of human neutrophils and its role in stimulated adhesion responses of these cells. J. Clin. Invest. 88, 2067–2076 (1991)

    Article  PubMed  CAS  Google Scholar 

  43. Liang, F., Seyrantepe, V., Landry, K., Ahmad, R., Ahmad, A., Stamatos, N.M., Pshezhetsky, A.V.: Monocyte differentiation up-regulates the expression of the lysosomal sialidase, Neu1, and triggers its targeting to the plasma membrane via major histocompatibility complex class II-positive compartments. J. Biol. Chem. 281, 27526–27538 (2006)

    Article  PubMed  CAS  Google Scholar 

  44. d’Azzo, A., Andria, G., Strisciuglio, G., Galjaard, H.: Galactosialidosis. In: Scriver, C.R., Beaudet, A.L., Sly, W.S., Valle, D. (eds.) The Metabolic and Molecular Bases of Inherited Disease, pp. 3811–3826. McGraw-Hill, New York (2001)

    Google Scholar 

  45. Bonten, E.J., Campos, Y., Zaitsev, V., Nourse, A., Waddell, B., Lewis, W., Taylor, G., d’Azzo, A.: Heterodimerization of the sialidase NEU1 with the chaperone protective protein/cathepsin A prevents its premature oligomerization. J. Biol. Chem. 284, 28430–28441 (2009)

    Article  PubMed  CAS  Google Scholar 

  46. Michalski, J.C., Strecker, G., Fournet, B., Cantz, M., Spranger, J.: Structures of sialyl-oligosaccharides excreted in the urine of a patient with mucolipidosis I. FEBS Lett. 79, 101–104 (1977)

    Article  PubMed  CAS  Google Scholar 

  47. Strecker, G., Peers, M.C., Michalski, J.C., Hondi-Assah, T., Fournet, B., Spik, G., Montreuil, J., Farriaux, J.P., Maroteaux, P., Durand, P.: Structure of nine sialyl-oligosaccharides accumulated in urine of eleven patients with three different types of sialidosis. Mucolipidosis II and two new types of mucolipidosis. Eur. J. Biochem. 72, 391–403 (1977)

    Article  Google Scholar 

  48. Dorland, L., Haverkamp, J., Viliegenthart, J.F., Strecker, G., Michalski, J.C., Fournet, B., Spik, G., Montreuil, J.: 360-MHz nuclear-magnetic-resonance spectroscopy of sialyl-oligosaccharides from patients with sialidosis (mucolipidosis I and II). Eur. J. Biochem. 87, 323–329 (1978)

    Article  PubMed  CAS  Google Scholar 

  49. van Pelt, J., Kamerling, J.P., Vliegenthart, J.F.G., Verheijen, F.W., Galjaard, H.: Isolation and structural characterization fof sialic acid-containing storage material from mucolipidosis I (sialidosis) fibroblasts. Biochem. Biophys. Acta. 965, 36–45 (1988)

    PubMed  Google Scholar 

  50. Yoshino, H., Miyashita, K., Miyatani, N., Ariga, T., Hashimoto, Y., Tsuji, S., Oyanagi, K., Ohama, E., Ikuta, F., Suzuki, A., et al.: Abnormal glycosphingolipid metabolism in the nervous system of galactosialidosis. J. Neurol. Sci. 97, 53–65 (1990)

    Article  PubMed  CAS  Google Scholar 

  51. Thomas, G.H.: Disorders of glycoprotein degradation: α-mannosidosis, β-mannosidosis, fucosidosis, and sialidosis. In: Scriver, C.R., Beaudet, A.L., Sly, W.S., Valle, D. (eds.) Metabolic and Molecular Bases of Inherited Disease, pp. 3507–3534. McGraw-Hill, New York (2001)

    Google Scholar 

  52. de Geest, N., Bonten, E., Mann, L., de Sousa-Hitzler, J., Hahn, C., d’Azzo, A.: Systemic and neurologic abnormalities distinguish the lysosomal disorders sialidosis and galactosialidosis in mice. Hum. Mol. Genet. 11, 1455–1464 (2002)

    Article  PubMed  Google Scholar 

  53. Zhou, X.Y., Morreau, H., Rottier, R., Davis, D., Bonten, E., Gillemans, N., Wenger, D., Grosveld, F.G., Doherty, P., Suzuki, K., Grosveld, G.C., d’Azzo, A.: Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells. Genes. Dev. 9, 2623–2634 (1995)

    Article  PubMed  CAS  Google Scholar 

  54. Womack, J.E., Yan, D.L., Potier, M.: Gene for neuraminidase activity on mouse chromosome 17 near h-2: pleiotropic effects on multiple hydrolases. Science 212, 63–65 (1981)

    Article  PubMed  CAS  Google Scholar 

  55. Carrillo, M.B., Milner, C.M., Ball, S.T., Snock, M., Campbell, R.D.: Cloning and characterization of a sialidase from the murine histocompatibility-2 complex: low levels of mRNA and a single amino acid mutation are responsible for reduced sialidase activity in mice carrying the Neu1a allele. Glycobiology 7, 975–986 (1997)

    Article  PubMed  CAS  Google Scholar 

  56. Rottier, R.J., Bonten, E., d’Azzo, A.: A point mutation in the neu-1 locus causes the neuraminidase defect in the SM/J mouse. Hum. Mol. Genet. 7, 313–321 (1998)

    Article  PubMed  CAS  Google Scholar 

  57. Champigny, M.J., Mitchell, M., Fox-Robichaud, A., Trigatti, B.L., Igdoura, S.A.: A point mutation in the neu1 promoter recruits an ectopic repressor, Nkx3.2 and results in a mouse model of sialidase deficiency. Mol. Genet. Metab. 97, 43–52 (2009)

    Article  PubMed  CAS  Google Scholar 

  58. Stinchcombe, J., Bossi, G., Griffiths, G.M.: Linking albinism and immunity: the secrets of secretory lysosomes. Science 305, 55–59 (2004)

    Article  PubMed  CAS  Google Scholar 

  59. Holt, O.J., Gallo, F., Griffiths, G.M.: Regulating secretory lysosomes. J. Biochem. 140, 7–12 (2006)

    Article  PubMed  CAS  Google Scholar 

  60. Yogalingam, G., Bonten, E.J., van de Vlekkert, D., Hu, H., Moshiach, S., Connell, S.A., d’Azzo, A.: Neuraminidase 1 is a negative regulator of lysosomal exocytosis. Dev. Cell. 15, 74–86 (2008)

    Article  PubMed  CAS  Google Scholar 

  61. Kima, P.E., Burleigh, B., Andrews, N.W.: Surface-targeted lysosomal membrane glycoprotein-1 (Lamp-1) enhances lysosome exocytosis and cell invasion by Trypanosoma cruzi. Cell. Microbiol. 2, 477–486 (2000)

    Article  PubMed  CAS  Google Scholar 

  62. Wu, X., Steigelman, K.A., Bonten, E., Hu, H., He, W., Ren, T., Zuo, J., d’Azzo, A.: Vacuolization and alterations of lysosomal membrane proteins in cochlear marginal cells contribute to hearing loss in neuraminidase 1-deficient mice. Biochim. Biophys. Acta. 1802, 259–268 (2010)

    PubMed  CAS  Google Scholar 

  63. Andrejewski, N., Punnonen, E.L., Guhde, G., Tanaka, Y., Lüllmann-Rauch, R., Hartmann, D., von Figura, K., Saftig, P.: Normal lysosomal morphology and function in LAMP-1-deficient mice. J. Biol. Chem. 274, 12692–12701 (1999)

    Article  PubMed  CAS  Google Scholar 

  64. Gaspar, E.B., Mortara, R.A., Andrade, L.O., da Silva, C.V.: Lysosomal exocytosis: an important event during invasion of lamp deficient cells by extracellular amastigotes of Trypanosoma cruzi. Biochem. Biophys. Res. Commun. 384, 265–269 (2009)

    Article  PubMed  CAS  Google Scholar 

  65. Babal, P., Janega, P., Cerna, A., Kholova, I., Brabencova, E.: Neoplastic transformation of the thyroid gland is accompanied by changes in cellular sialylation. Acta Histochem. 108, 133–140 (2006)

    Article  PubMed  CAS  Google Scholar 

  66. Berbec, H., Paszkowska, A., Siwek, B., Gradziel, K., Cybulski, M.: Total serum sialic acid concentration as a supporting marker of malignancy in ovarian neoplasia. Eur. J. Gynaecol. Oncol. 20, 389–392 (1999)

    PubMed  CAS  Google Scholar 

  67. Brooks, S.A., Leathem, A.J.C.: Expression of N-acetyl galactosaminylated and sialylated glycans by metastases arising from primary breast cancer. Invasion Metastasis 18, 115–121 (1999)

    Article  CAS  Google Scholar 

  68. Feijoo-Carnero, C., Rodriguez-Berrocal, F.J., de la Cadena, M.N., Ayude, D., de Carlos, A., Martinez-Zorzano, V.S.: Clinical significance of preoperative serum sialic acid levels in colorectal cancer: utility in the detection of patients at high risk of tumor recurrence. Int. J. Biol. Markers 19, 38–45 (2004)

    PubMed  CAS  Google Scholar 

  69. Basoglu, M., Yildirgan, M.I., Taysi, S., Yilmaz, I., Kiziltunc, A., Balik, A.A., Celebi, F., Atamanalp, S.S.: Levels of soluble intercellular adhesion molecule-1 and total sialic acid in serum of patients with colorectal cancer. J. Surg. Oncol. 83, 180–184 (2003)

    Article  PubMed  CAS  Google Scholar 

  70. Rajpura, K.B., Patel, P.S., Chawda, J.G., Shah, R.M.: Clinical significance of total and lipid bound sialic acid levels in oral pre-cancerous conditions and oral cancer. J. Oral Pathol. Med. 34, 263–267 (2005)

    Article  PubMed  CAS  Google Scholar 

  71. Romppanen, J., Haapalainen, T., Punonen, K., Penttila, I.: Serum sialic acid and prostate-specific antigen in differential diagnosis of benign prostate hyperplasia and prostate cancer. Anticancer Res. 22, 415–420 (2002)

    PubMed  Google Scholar 

  72. Uslu, C., Taysi, S., Akcay, F., Sutbeyaz, M.Y., Bakan, N.: Serum free and bound sialic acid and α-1-acid glycoprotein in patients with laryngeal cancer. Ann. Clin. Lab. Sci. 33, 156–159 (2003)

    PubMed  CAS  Google Scholar 

  73. Lijima, S., Shiba, K., Kimura, M., Nagai, K., Iwai, T.: Changes of α1-acid glycoprotein microheterogeneity in acute inflammation stages analyzed by isoelectric focusing using serum obtained postoperatively. Electrophoresis 21, 753–759 (2000)

    Article  Google Scholar 

  74. Herve, F., Duche, J.C., Jaurand, M.C.: Changes in expression and microheterogeneity of the genetic variants of human α1-acid glycoprotein in malignant mesothelioma. J. Chromatogr. B 715, 111–123 (1998)

    Article  CAS  Google Scholar 

  75. Miyagi, T., Wada, T., Yamaguchi, K., Hata, K.: Sialidase and malignancy: a minireview. Glycoconj. J. 20, 189–198 (2004)

    Article  PubMed  CAS  Google Scholar 

  76. Miyagi, T.: Aberrant expression of sialidase and cancer progression. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 84, 407–418 (2008)

    Article  PubMed  CAS  Google Scholar 

  77. Miyagi, T., Sato, K., Hata, K., Taniguchi, S.: Metastatic potential of transformed rat 3Y1 cell lines is inversely correlated with lysosomal-type sialidase activity. FEBS Lett. 349, 255–259 (1994)

    Article  PubMed  CAS  Google Scholar 

  78. Sawada, M., Moriya, S., Saito, S., Shineha, R., Satomi, S., Yamori, T., Tsuruo, T., Kannagi, R., Miyagi, T.: Reduced sialidase expression in highly metastatic variants of mouse colon adenocarcinoma 26 and retardation of their metastatic ability by sialidase overexpression. Int. J. Cancer 97, 180–185 (2002)

    Article  PubMed  CAS  Google Scholar 

  79. Kato, T., Wang, Y., Yamaguchi, K., Milner, C.M., Shineha, R., Satomi, S., Miyagi, T.: Overexpressing of lysosomal-type sialidase leads to suppression of metastasis associated with reversion of malignant phenotype in murine B16 melanoma cells. Int. J. Cancer 92, 797–804 (2001)

    Article  PubMed  CAS  Google Scholar 

  80. Uemura, T., Shiozaki, K., Yamaguchi, K., Miyazaki, S., Satomi, S., Kato, K., Sakuraba, H., Miyagi, T.: Contribution of sialidase NEU1 to suppression of metastasis of human colon cancer cells through desialylation of integrin beta4. Oncogene 28, 1218–1229 (2009)

    Article  PubMed  CAS  Google Scholar 

  81. Frohman, M., Cowing, C.: Presentation of antigen by B cells: functional dependence on radiation dose, interleukins, cellular activation, and differential glycosylation. J. Immunol. 134, 2269–2275 (1985)

    PubMed  CAS  Google Scholar 

  82. Kearse, K.P., Cassatt, D.R., Kaplan, A.M., Cohen, D.A.: The requirement for surface Ig signaling as a prerequisite for T cell:B cell interactions. A possible role for desialylation. J. Immunol. 140, 1770–1778 (1988)

    PubMed  CAS  Google Scholar 

  83. Krieger, J., Jenis, D.M., Chesnut, R.W., Grey, H.M.: Studies on the capacity of intact cells and purified Ia from different B cell sources to function in antigen presentation to T cells. J. Immunol. 140, 388–394 (1988)

    PubMed  CAS  Google Scholar 

  84. Baum, L.G., Derbin, K., Perillo, N.L., Wu, T., Pang, M., Uittenbogaart, C.: Characterization of terminal sialic acid linkages on human thymocytes. Correlation between lectin-binding phenotype and sialyltransferase expression. J. Biol. Chem. 271, 10793–10799 (1996)

    Article  PubMed  CAS  Google Scholar 

  85. Bagriaçik, E.U., Miller, K.S.: Cell surface sialic acid and the regulation of immune cell interactions: the neuraminidase effect reconsidered. Glycobiology 9, 267–275 (1999)

    Article  PubMed  Google Scholar 

  86. Watanabe, Y., Shiratsuchi, A., Shimizu, K., Takizawa, T., Nakanishi, Y.: Stimulation of phagocytosis of influenza virus-infected cells through surface desialylation of macrophages by viral neuraminidase. Microbiol. Immunol. 48, 875–881 (2004)

    PubMed  CAS  Google Scholar 

  87. Landolfi, N.F., Cook, R.G.: Activated T lymphocytes express class I molecules which are hyposialylated compared to other lymphocyte populations. Mol. Immunol. 23, 297–309 (1986)

    Article  PubMed  CAS  Google Scholar 

  88. Chen, X.P., Enioutina, E.Y., Daynes, R.A.: The control of IL-4 gene expression in activated murine T lymphocytes: a novel role for neu-1 sialidase. J. Immunol. 158, 3070–3080 (1997)

    PubMed  CAS  Google Scholar 

  89. Chen, X.P., Ding, X., Daynes, R.A.: Ganglioside control over IL-4 priming and cytokine production in activated T cells. Cytokine 12, 972–985 (2000)

    Article  PubMed  CAS  Google Scholar 

  90. Yamamoto, N., Kumashiro, R.: Conversion of vitamin D3 binding protein (group-specific component) to a macrophage activating factor by the stepwise action of beta-galactosidase of B cells and sialidase of T cells. J. Immunol. 151, 2794–2802 (1993)

    PubMed  CAS  Google Scholar 

  91. Naraparaju, V.R., Yamamoto, N.: Roles of beta-galactosidase of B lymphocytes and sialidase of T lymphocytes in inflammation-primed activation of macrophages. Immunol. Lett. 43, 143–148 (1994)

    Article  PubMed  CAS  Google Scholar 

  92. Landolfi, N.F., Leone, J., Womack, J.E., Cook, R.G.: Activation of T lymphocytes results in an increase in H-2-encoded neuraminidase. Immunogenetics 22, 159–167 (1985)

    Article  PubMed  CAS  Google Scholar 

  93. Nan, X., Carubelli, I., Stamatos, N.M.: Sialidase expression in activated human T lymphocytes influences production of IFN-gamma. J. Leukoc. Biol. 81, 284–296 (2007)

    Article  PubMed  CAS  Google Scholar 

  94. Stamatos, N.M., Liang, F., Nan, X., Landry, K., Cross, A.S., Wang, L.X., Pshezhetsky, A.V.: Differential expression of endogenous sialidases of human monocytes during cellular differentiation into macrophages. FEBS J. 272, 2545–2556 (2005)

    Article  PubMed  CAS  Google Scholar 

  95. Seyrantepe, V., Hinek, A., Peng, J., Fedjaev, M., Ernest, S., Kadota, Y., Canuel, M., Itoh, K., Morales, C.R., Lavoie, J., Tremblay, J., Pshezhetsky, A.V.: Circulation 117, 1973–1981 (2008)

    Article  PubMed  CAS  Google Scholar 

  96. Seyrantepe, V., Iannello, A., Liang, F., Kanshin, E., Jayanth, P., Samarani, S., Szewczuk, M.R., Ahmad, A., Pshezhetsky, A.V.: Regulation of phagocytosis in macrophages by neuraminidase 1. J. Biol. Chem. 285, 206–215 (2010)

    Article  PubMed  CAS  Google Scholar 

  97. Amith, S.R., Jayanth, P., Franchuk, S., Siddiqui, S., Seyrantepe, V., Gee, K., Basta, S., Beyaert, R., Pshezhetsky, A.V., Szewczuk, M.R.: Dependence of pathogen molecule-induced toll-like receptor activation and cell function on Neu1 sialidase. Glycoconj. J. 26, 1197–1212 (2009)

    Article  PubMed  CAS  Google Scholar 

  98. Amith, S.R., Jayanth, P., Franchuk, S., Finlay, T., Seyrantepe, V., Beyaert, R., Pshezhetsky, A.V., Szewczuk, M.R.: Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling. Cell. Signal. 22, 314–324 (2010)

    Article  PubMed  CAS  Google Scholar 

  99. Hata, K., Koseki, K., Yamaguchi, K., Moriya, S., Suzuki, Y., Yingsakmongkon, S., Hirai, G., Sodeoka, M., von Itzstein, M., Miyagi, T.: Limited inhibitory effects of oseltamivir and zanamivir on human sialidases. Antimicrob. Agents Chemother. 52, 3484–3491 (2008)

    Article  PubMed  CAS  Google Scholar 

  100. Jayanth, P., Amith, S.R., Gee, K., Szewczuk, M.R.: Neu1 sialidase and matrix metalloproteinase-9 cross-talk is essential for neurotrophin activation of Trk receptors and cellular signaling. Cell. Signal. 22, 1193–1205 (2010)

    Article  PubMed  CAS  Google Scholar 

  101. Stamatos, N.M., Carubelli, I., van de Vlekkert, D., Bonten, E.J., Papini, N., Feng, C., Venerando, B., d’Azzo, A., Cross, A.S., Wang, L.X., Gomatos, P.J.: LPS-induced cytokine production in human dendritic cells is regulated by sialidase activity. J. Leukoc. Biol. 88, 1227–1239 (2010)

    Article  PubMed  CAS  Google Scholar 

  102. Gross, N., Balmas, K., Beretta Brognara, C.: Role of CD44H carbohydrate structure in neuroblastoma adhesive properties. Med. Pediatr. Oncol. 36, 139–141 (2001)

    Article  PubMed  CAS  Google Scholar 

  103. Nightingale, T.D., Frayne, M.E., Clasper, S., Banerji, S., Jackson, D.G.: A mechanism of sialylation functionally silences the hyaluronan receptor LYVE-1 in lymphatic endothelium. J. Biol. Chem. 284, 3935–3945 (2009)

    Article  PubMed  CAS  Google Scholar 

  104. Katoh, S., Maeda, S., Fukuoka, H., Wada, T., Moriya, S., Mori, A., Yamaguchi, K., Senda, S., Miyagi, T.: A crucial role of sialidase Neu1 in hyaluronan receptor function of CD44 in T helper type 2-mediated airway inflammation of murine acute asthmatic model. Clin. Exp. Immunol. 161, 233–241 (2010)

    PubMed  CAS  Google Scholar 

  105. Morreau, H., Galjart, N.J., Gillemans, N., Willemsen, R., van der Horst, G.T., d’Azzo, A.: Alternative splicing of 3′-Galactosidase mRNA generates the classic lysosomal enzyme and a related protein 3-Galactosidase. J. Biol. Chem. 264, 20655–20663 (1989)

    PubMed  CAS  Google Scholar 

  106. Hinek, A., Wrenn, D.S., Mecham, R.P., Barondes, S.H.: The elastin receptor: a galactoside-binding protein. Science 239, 1539–1541 (1988)

    Article  PubMed  CAS  Google Scholar 

  107. Hinek, A., Rabinovitch, M., Keeley, F., Okamura, O.Y., Callahan, J.W.: The 67 kD elastin/laminin-binding protein is related to an alternatively spliced β-galactosidase. J. Clin. Invest. 91, 1198–1205 (1993)

    Article  PubMed  CAS  Google Scholar 

  108. Hinek, A.: Nature and multiple functions of the 67 kD elastin/laminin binding protein. Cell Adhes. Commun. 2, 185–193 (1994)

    Article  PubMed  CAS  Google Scholar 

  109. Privitera, S., Prody, C.A., Callahan, J.W., Hinek, A.: The 67-kDa enzymatically inactive alternatively spliced variant of β-galactosidase is identical to the elastin/laminin-binding protein. J. Biol. Chem. 273, 6319–6326 (1998)

    Article  PubMed  CAS  Google Scholar 

  110. Hinek, A., Pshezhetsky, A.V., von Itzstein, M., Starcher, B.: Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly. J. Biol. Chem. 281, 3698–3710 (2006)

    Article  PubMed  CAS  Google Scholar 

  111. Hinek, A., Smith, A.C., Cutiongco, E.M., Callahan, J.W., Gripp, K.W., Weksberg, R.: Decreased elastin deposition and high proliferation of fibroblasts from Costello syndrome are related to functional deficiency in the 67-kD elastin-binding protein. Am. J. Hum. Genet. 66, 859–872 (2000)

    Article  PubMed  CAS  Google Scholar 

  112. Caciotti, A., Donati, M.A., Bardelli, T., d’Azzo, A., Massai, G., Luciani, L., Zammarchi, E., Morrone, A.: Primary and secondary elastin-binding protein defect leads to impaired elastogenesis in fibroblasts from GM1-gangliosidosis patients. Am. J. Pathol. 167, 1689–1698 (2005)

    Article  PubMed  CAS  Google Scholar 

  113. Factor, S.M., Biempica, L., Goldfischer, S.: Coronary intimal sclerosis in Morquio’s syndrome. Virchows Arch. A Pathol. Anat. Histol. 379, 1–10 (1978)

    Article  PubMed  CAS  Google Scholar 

  114. Dangel, J.H.: Cardiovascular changes in children with mucopolysaccharide storage diseases and related disorders–clinical and echocardiographic findings in 64 patients. Eur. J. Pediatr. 157, 534–538 (1998)

    Article  PubMed  CAS  Google Scholar 

  115. Guertl, B., Noehammer, C., Hoefler, G.: Metabolic cardiomyopathies. Int. J. Exp. Pathol. 81, 349–372 (2000)

    Article  PubMed  CAS  Google Scholar 

  116. Starcher, B., d’Azzo, A., Keller, P.W., Rao, G.K., Nadarajah, D., Hinek, A.: Neuraminidase-1 is required for the normal assembly of elastic fibers. Am. J. Physiol. Lung Cell. Mol. Physiol. 295, L637–L647 (2008)

    Article  PubMed  CAS  Google Scholar 

  117. Hinek, A., Bodnaruk, T.D., Bunda, S., Wang, Y., Liu, K.: Neuraminidase-1, a subunit of the cell surface elastin receptor, desialylates and functionally inactivates adjacent receptors interacting with the mitogenic growth factors PDGF-BB and IGF-II. Am. J. Pathol. 173, 1042–1056 (2008)

    Article  PubMed  CAS  Google Scholar 

  118. Myllarniemi, M., Calderon, L., Lemstrom, K., Buchdunger, E., Hayry, P.: Inhibition of platelet-derived growth factor receptor tyrosine kinase inhibits vascular smooth muscle cell migration and proliferation. FASEB J. 11, 1119–1126 (1997)

    PubMed  CAS  Google Scholar 

  119. Bayes-Genis, A., Conover, C.A., Schwartz, R.S.: The insulin-like growth factor axis: A review of atherosclerosis and restenosis. Circ. Res. 86, 125–130 (2000)

    PubMed  CAS  Google Scholar 

  120. Zaina, S., Pettersson, L., Ahren, B., Branen, L., Hassan, A.B., Lindholm, M., Mattsson, R., Thyberg, J., Nilsson, J.: Insulin-like growth factor II plays a central role in atherosclerosis mouse model. J. Biol. Chem. 277, 4504–4511 (2002)

    Article  CAS  Google Scholar 

  121. Zaina, S., Nilsson, J.: Insulin-like growth factor II and its receptors in atherosclerosis and in conditions predisposing to atherosclerosis. Curr. Opin. Lipidol. 14, 483–489 (2003)

    Article  PubMed  CAS  Google Scholar 

  122. Tallquist, M., Kazlauskas, A.: PDGF signaling in cells and mice. Cytokine Growth Factor Rev. 15, 205–213 (2004)

    Article  PubMed  CAS  Google Scholar 

  123. Arabkhari, M., Bunda, S., Wang, Y., Wang, A., Pshezhetsky, A.V., Hinek, A.: Desialylation of insulin receptors and IGF-1 receptors by neuraminidase-1 controls the net proliferative response of L6 myoblasts to insulin. Glycobiology 20, 603–616 (2010)

    Article  PubMed  CAS  Google Scholar 

  124. Champigny, M.J., Perry, R., Rudnicki, M., Igdoura, S.A.: Overexpression of MyoD-inducible lysosomal sialidase (neu1) inhibits myogenesis in C2C12 cells. Exp. Cell Res. 311, 157–166 (2005)

    Article  PubMed  CAS  Google Scholar 

  125. Zanoteli, E., van de Vlekkert, D., Bonten, E.J., Hu, H., Mann, L., Gomero, E.M., Harris, A.J., Ghersi, G., d’Azzo, A.: Muscle degeneration in neuraminidase 1-deficient mice results from infiltration of the muscle fibers by expanded connective tissue. Biochim. Biophys. Acta 1802, 659–672 (2010)

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the operating grants from the Canadian Institutes of Health Research to A.V.P. and A.H. and by the operating grant from the Canadian Diabetes Association to A.V.P. The authors thank Dr. L. Ashmarina for critical reading of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alexey V. Pshezhetsky.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pshezhetsky, A.V., Hinek, A. Where catabolism meets signalling: neuraminidase 1 as a modulator of cell receptors. Glycoconj J 28, 441–452 (2011). https://doi.org/10.1007/s10719-011-9350-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-011-9350-5

Keywords

Navigation