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Cell-surface arylsulfatase A and B on sinusoidal endothelial cells, hepatocytes, and Kupffer cells in mammalian livers

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Abstract

Arylsulfatase A (ARSA) and B (ARSB) have been regarded as lysosomal enzymes because of their hydrolytic activity on synthetic aromatic substrates and the lysosomal localization of their enzymatic activity. Using sea urchin embryos, we previously demonstrated that the bulk of ARS is located on the cell surface of the epithelium, colocalizing with sulfated polysaccharides, and that it does not exhibit enzymatic activity. To examine whether ARSA and ARSB exist on the cell surface in mammalian tissues, we raised antibodies against ARSA and ARSB and examined immunohistochemically their localization in the liver using light and electron microscopy. Here we show that mammalian ARSA and ARSB exist on the cell surface of sinusoidal endothelial cells, hepatocytes, and sinusoidal macrophages (Kupffer cells), as well as in the lysosome. They are also colocalized with heparan sulfate proteoglycan. These results suggest that ARSA and ARSB also may function in the cell surface of mammals. This is the first report to show cell-surface localization of ARS in mammalian somatic cells. The extracellular localization of ARS will provide new insight for human ARS deficiency disorders, such as metachromatic leukodystrophy and mucopolysaccharidosis VI.

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References

  1. Sardiello M, Annunziata I, Roma G, Ballabio A (2005) Sulfatases and sulfatase modifying factors: an exclusive and promiscuous relationship. Hum Mol Genet 14:3203–3217

    Article  PubMed  CAS  Google Scholar 

  2. Obaya AJ (2006) Molecular cloning and initial characterization of three novel human sulfatases. Gene 372:110–117

    Article  PubMed  CAS  Google Scholar 

  3. Diez-Roux G, Ballabio A (2005) Sulfatases and human disease. Annu Rev Genomics Hum Genet 6:355–379

    Article  PubMed  CAS  Google Scholar 

  4. Gieselmann V, Matzner U, Hess B, Lüllmann-Rauch R, Coenen R, Hartmann D, D’Hooge R, DeDeyn P, Nagels G (1998) Metachromatic leukodystrophy: molecular genetics and an animal model. J Inherit Metab Dis 21:564–574

    Article  PubMed  CAS  Google Scholar 

  5. Gieselmann V (2003) Metachromatic leukodystrophy: recent research developments. J Child Neurol 18:591–595

    Article  PubMed  Google Scholar 

  6. Yogalingam G, Litjens T, Bielicki J, Crawley AC, Muller V, Anson DS, Hopwood JJ (1996) Feline mucopolysaccharidosis type VI. Characterization of recombinant N-acetylgalactosamine 4-sulfatase and identification of a mutation causing the disease. J Biol Chem 271:27259–27265

    Article  PubMed  CAS  Google Scholar 

  7. Neufeld EF, Muenzer J (2001) The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York, pp 3421–3452

    Google Scholar 

  8. Litjens T, Hopwood JJ (2001) Mucopolysaccharidosis type VI: structural and clinical implications of mutations in N-acetylgalactosamine-4-sulfatase. Hum Mutat 18:282–295

    Article  PubMed  CAS  Google Scholar 

  9. Koppe JG, Marinkovic-Ilsen A, Rijken Y, De Groot WP, Jöbsis AC (1978) X-linked ichthyosis: a sulphatase deficiency. Arch Dis Child 53:803–806

    Article  PubMed  CAS  Google Scholar 

  10. Hopsu-Havu VK, Arstila AU, Helminen HJ, Kalino HÖ (1967) Improvements in the method for the electron microscopic localization of arylsulfatase activity. Histochemie 8:54–64

    PubMed  CAS  Google Scholar 

  11. Seljelid R, Helminen HJ (1968) The localization of aryl sulfatase activity in thyroid follicle cells. J Histochem Cytochem 16:467–472

    PubMed  CAS  Google Scholar 

  12. Kawano J, Aikawa E (1987) Ultrastructural localization of arylsulfatase C activity in rat kidney. J Histochem Cytochem 35:523–530

    PubMed  CAS  Google Scholar 

  13. Jöbsis AC, De Groot WP, Tigges AJ, De Bruijn HW, Rijken Y, Meijer AE, Marinkovic-Ilsen A (1980) X-linked ichthyosis and Xlinked placental sulfatase deficiency: a disease entity. Histochemical observations. Am J Pathol 99:279–289

    PubMed  Google Scholar 

  14. Daniele A, Parenti G, d’Addio M, Andria G, Ballabio A, Meroni G (1998) Biochemical characterization of arylsulfatase E and functional analysis of mutations found in patients with X-linked chondrodysplasia punctata. Am J Hum Genet 62:562–572

    Article  PubMed  CAS  Google Scholar 

  15. Hanson SR, Best MD, Wong CH (2004) Sulfatases: structure, mechanism, biological activity, inhibition, and synthetic utility. Angew Chem Int Ed Eng 43:5736–5763

    Article  CAS  Google Scholar 

  16. Frese M-A, Schulz S, Dierks T (2008) Arylsulfatase G, a novel lysosomal sulfatase. J Biol Chem 283:11388–11395

    Article  PubMed  CAS  Google Scholar 

  17. Mitsunaga-Nakatsubo K, Akasaka K, Akimoto Y, Akiba E, Kitajima T, Tomita M, Hirano H, Shimada H (1998) Arylsulfatase exists as non-enzymatic cell surface protein in sea urchin embryos. J Exp Zool 280:220–230

    Article  PubMed  CAS  Google Scholar 

  18. Peters C, Schmidt B, Rommerskirch W, Rupp K, Zühlsdorf M, Vingron M, Meyer HE, Pohlmann R, von Figura K (1990) Phylogenetic conservation of arylsulfatases. cDNA cloning and expression of human arylsulfatase B. J Biol Chem 265:3374–3381

    PubMed  CAS  Google Scholar 

  19. Akimoto Y, Yamakawa N, Furukawa K, Kimata K, Kawakami H, Hirano H (2002) Changes in distribution of the long form of type XII collagen during chicken corneal development. J Histochem Cytochem 50:851–862

    PubMed  CAS  Google Scholar 

  20. Bond CS, Clements PR, Ashby SJ, Collyer CA, Harrop SJ, Hopwood JJ, Guss JM (1997) Structure of a human lysosomal sulfatase. Structure 5:277–289

    Article  PubMed  CAS  Google Scholar 

  21. Evers M, Saftig P, Schmidt P, Hafner A, McLoghlin DB, Schmahl W, Hess B, von Figura K, Peters C (1996) Targeted disruption of the arylsulfatase B gene results in mice resembling the phenotype of mucopolysaccharidosis VI. Proc Natl Acad Sci USA 93:8214–8219

    Article  PubMed  CAS  Google Scholar 

  22. Stein C, Gieselmann V, Kreysing J, Schmidt B, Pohlmann R, Waheed A, Meyer HE, O’Brien JS, von Figura K (1989) Cloning and expression of human arylsulfatase A. J Biol Chem 264:1252–1259

    PubMed  CAS  Google Scholar 

  23. Ngernosoungnern A, Weerachatyanukul W, Saewu A, Thitilertdecha S, Sobhon P, Sretarugsa P (2004) Rat sperm AS-A: subcellular localization in testis and epididymis and surface distribution in epididymal sperm. Cell Tissue Res 318:353–363

    Article  Google Scholar 

  24. Wu A, Anupriwan A, Iamsaard S, Chakrabandhu K, Santos DC, Rupar T, Tsang BK, Carmona E, Tanphaichitr N (2007) Sperm surface arylsulfatase A can disperse the cumulus matrix of cumulus oocyte complexes. J Cell Physiol 213:201–211

    Article  PubMed  CAS  Google Scholar 

  25. Sasaki H, Akasaka K, Shimada H, Shiroya T (1987) Purification and characterization of arylsulfatase from sea urchin embryo. Comp Biochem Biophys 88B:147–152

    Article  CAS  Google Scholar 

  26. Ghosh D (2007) Human sulfatases: a structural perspective to catalysis. Cell Mol Life Sci 64:2013–2022

    Article  PubMed  CAS  Google Scholar 

  27. Kawano J, Kotani T, Umeki K, Oinuma T, Ohtaki S, Aikawa E (1989) A monoclonal antibody to rat liver arylsulfatase C and its application in immunohistochemistry. J Histochem Cytochem 37:683–690

    PubMed  CAS  Google Scholar 

  28. Mehl E, Jatzkewitz H (1968) Cerebroside 3-sulfate as a physiological substrate of arylsulfatase A. Biochim Biophys Acta 151:619–627

    PubMed  CAS  Google Scholar 

  29. Yogalingam G, Litjens T, Bielicki J, Crawley AC, Muller V, Anson DS, Hopwood JJ (1996) Feline mucopolysaccharidosis type VI. Characterization of recombinant N-acetylgalactosamine 4-sulfatase and identification of a mutation causing the disease. J Biol Chem 271:27259–27265

    Article  PubMed  CAS  Google Scholar 

  30. Dhoot GK, Gustafsson MK, Ai X, Sun W, Standiford DM, Emerson CP Jr (2001) Regulation of Wnt signaling and embryo patterning by an extracellular sulfatase. Science 293:1663–1666

    Article  PubMed  CAS  Google Scholar 

  31. Morimoto-Tomita M, Uchimura K, Werb Z, Hemmerich S, Rosen SD (2002) Cloning and characterization of two extracellular heparin-degrading endosulfatases in mice and humans. J Biol Chem 277:49175–49185

    Article  PubMed  CAS  Google Scholar 

  32. Sasaki H, Yamada K, Akasaka K, Kawasaki H, Suzuki K, Saito A, Sato M, Shimada, H (1988) cDNA cloning, nucleotide sequence and expression of the gene for arylsulfatase in the sea urchin (Hemicentrotus pulcherrimus) embryo. Eur J Biochem 177:9–13

    Article  PubMed  CAS  Google Scholar 

  33. Rapraeger AC, Epel D (1981) The appearance of an extracellular arylsulfatase during morphogenesis of the sea urchin Strongylocentrotus purpuratus. Dev Biol 88:269–278

    Article  PubMed  CAS  Google Scholar 

  34. Akasaka K, Terayama H (1983) Sulfated glycan present in the EDTA extract of Hemicentrotus embryos (mid-gastrula). Exp Cell Res 146:177–185

    Article  PubMed  CAS  Google Scholar 

  35. Akasaka K, Terayama H (1984) A proteoglycan fraction isolated from the EDTA extract of sea urchin (Hemicentrotus pulcherrimus) gastrulae stimulates reaggregation of dissociated embryonic cells. Exp Cell Res 150:226–233

    Article  PubMed  CAS  Google Scholar 

  36. Akasaka K, Akimoto Y, Sato M, Hirano H, Shimada H (1990) Histochemical detection of arylsulfatase activity in sea urchin embryos. Dev Growth Differ 32:293–298

    Article  Google Scholar 

  37. Akasaka K, Uemoto H, Wilt F, Mitsunaga-Nakatsubo K, Shimada H (1997) Oral-aboral ectoderm differentiation of sea urchin embryos is disrupted in response to calcium ionophore. Dev Growth Differ 39:373–379

    Article  PubMed  CAS  Google Scholar 

  38. Haag ES, Raff RA (1998) Isolation and characterization of three mRNAs enriched in embryos of the direct-developing sea urchin Heliocidaris erythrogramma: evolution of larval ectoderm. Dev Genes Evol 208:188–204

    Article  PubMed  CAS  Google Scholar 

  39. Steckel F, Hasilik A, von Figura K (1983) Biosynthesis and maturation of arylsulfatase B in normal and mutant cultured human fibroblasts. J Biol Chem 258:14322–14326

    PubMed  CAS  Google Scholar 

  40. Sommerlade HJ, Selmer T, Ingendoh A, Gieselmann V, von Figura K, Neifer K, Schmidt B (1994) Glycosylation and phosphorylation of arylsulfatase A. J Biol Chem 269:20977–20981

    PubMed  CAS  Google Scholar 

  41. Laidler P, Litynska A (1997) Arylsulfatase A from human placenta possesses only high mannose-type glycans. Int J Biochem Cell Biol 29:475–483

    Article  PubMed  CAS  Google Scholar 

  42. Stein M, Zijderhand-Bleekemolen JE, Geuze H, Hasilik A, von Figura K (1987) Mr 46,000 mannose 6-phosphate specific receptor: its role in targeting of lysosomal enzymes. EMBO J 6:2677–2681

    PubMed  CAS  Google Scholar 

  43. Chao HH, Waheed A, Pohlmann R, Hille A, von Figura K (1990) Mannose 6-phosphate receptor dependent secretion of lysosomal enzymes. EMBO J 9:3507–3513

    PubMed  CAS  Google Scholar 

  44. Ghosh P, Dahns NM, Kornfeld S (2003) Mannose 6-phosphate receptors: new twists in the tale. Nat Rev Mol Cell Biol 4:202–212

    Article  PubMed  CAS  Google Scholar 

  45. Geuze HJ, Slot JW, Strous GJ, Hasilik A, Von Figura K (1984) Ultrastructural localization of the mannose 6-phosphate receptor in rat liver. J Cell Biol 98:2047–2054

    Article  PubMed  CAS  Google Scholar 

  46. Yoshida M, Noguchi J, Ikadai H, Takahashi M, Nagase S (1993) Arylsulfatase B-deficient mucopolysaccharidosis in rats. J Clin Invest 91:1099–1104

    Article  PubMed  CAS  Google Scholar 

  47. Yoshida M, Ikadai H, Maekawa A, Takahashi M, Nagase S (1993) Pathological characteristics of mucopolysaccharidosis VI in the rat. J Comp Pathol 109:141–153

    Article  PubMed  CAS  Google Scholar 

  48. Hess B, Saftig P, Hartmann D, Coenen R, Lüllmann-Rauch R, Goebel HH, Evers M, von Figura K, D’Hooge R, Nagels G, De Deyn P, Peters C, Gieselmann V (1996) Phenotype of arylsulfatase A-deficient mice: relationship to human metachromatic leukodystrophy. Proc Natl Acad Sci USA 93:14821–14826

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan

    Keiko Mitsunaga-Nakatsubo

  2. LSL, Tokyo, Japan

    Shinichiro Kusunoki

  3. Department of Anatomy, Kyorin University School of Medicine, Shinkawa, Mitaka, Tokyo, 181-8611, Japan

    Hayato Kawakami & Yoshihiro Akimoto

  4. MMBS, Graduate School of Sciences, University of Tokyo, Kanagawa, Japan

    Koji Akasaka

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  1. Keiko Mitsunaga-Nakatsubo
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  2. Shinichiro Kusunoki
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  3. Hayato Kawakami
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  4. Koji Akasaka
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  5. Yoshihiro Akimoto
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Correspondence to Yoshihiro Akimoto.

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Mitsunaga-Nakatsubo, K., Kusunoki, S., Kawakami, H. et al. Cell-surface arylsulfatase A and B on sinusoidal endothelial cells, hepatocytes, and Kupffer cells in mammalian livers. Med Mol Morphol 42, 63–69 (2009). https://doi.org/10.1007/s00795-009-0447-x

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  • DOI: https://doi.org/10.1007/s00795-009-0447-x

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