Cellular and Molecular Life Sciences

, Volume 67, Issue 5, pp 769–780 | Cite as

Sulfatase activities towards the regulation of cell metabolism and signaling in mammals

  • M. Buono
  • Maria Pia Cosma


In higher vertebrates, sulfatases belong to a conserved family of enzymes that are involved in the regulation of cell metabolism and in developmental cell signaling. They cleave the sulfate from sulfate esters contained in hormones, proteins, and complex macromolecules. A highly conserved cysteine in their active site is post-translationally converted into formylglycine by the formylglycine-generating enzyme encoded by SUMF1 (sulfatase modifying factor 1). This post-translational modification activates all sulfatases. Sulfatases are extensively glycosylated proteins and some of them follow trafficking pathways through cells, being secreted and taken up by distant cells. Many proteoglycans, glycoproteins, and glycolipids contain sulfated carbohydrates, which are sulfatase substrates. Indeed, sulfatases operate as decoding factors for a large amount of biological information contained in the structures of the sulfated sugar chains that are covalently linked to proteins and lipids. Modifications to these sulfate groups have pivotal roles in modulating specific signaling pathways and cell metabolism in mammals.


Sulfatases Sulfatase modifying factor 1 Multiple sulfatase deficiency Lysosomal storage disease Cell signaling 



The authors thank G. Diez-Roux and D. Di Bernardo for critical reading of the manuscript.


  1. 1.
    Diez-Roux G, Ballabio A (2005) Sulfatases and human disease. Annu Rev Genomics Hum Genet 6:355–379PubMedCrossRefGoogle Scholar
  2. 2.
    Sardiello M, Annunziata I, Roma G, Ballabio A (2005) Sulfatases and sulfatase modifying factors: an exclusive and promiscuous relationship. Hum Mol Genet 14:3203–3217PubMedCrossRefGoogle Scholar
  3. 3.
    Dierks T, Lecca MR, Schlotterhose P, Schmidt B, von Figura K (1999) Sequence determinants directing conversion of cysteine to formylglycine in eukaryotic sulfatases. EMBO J 18:2084–2091PubMedCrossRefGoogle Scholar
  4. 4.
    Landgrebe J, Dierks T, Schmidt B, von Figura K (2003) The human SUMF1 gene, required for posttranslational sulfatase modification, defines a new gene family which is conserved from pro- to eukaryotes. Gene 316:47–56PubMedCrossRefGoogle Scholar
  5. 5.
    Recksiek M, Selmer T, Dierks T, Schmidt B, von Figura K (1998) Sulfatases, trapping of the sulfated enzyme intermediate by substituting the active site formylglycine. J Biol Chem 273:6096–6103PubMedCrossRefGoogle Scholar
  6. 6.
    Waldow A, Schmidt B, Dierks T, von Bulow R, von Figura K (1999) Amino acid residues forming the active site of arylsulfatase A. Role in catalytic activity and substrate binding. J Biol Chem 274:12284–12288PubMedCrossRefGoogle Scholar
  7. 7.
    Hanson SR, Best MD, Wong CH (2004) Sulfatases: structure, mechanism, biological activity, inhibition, and synthetic utility. Angew Chem Int Ed Engl 43:5736–5763PubMedCrossRefGoogle Scholar
  8. 8.
    Lukatela G, Krauss N, Theis K, Selmer T, Gieselmann V, von Figura K, Saenger W (1998) Crystal structure of human arylsulfatase A: the aldehyde function and the metal ion at the active site suggest a novel mechanism for sulfate ester hydrolysis. Biochemistry 37:3654–3664PubMedCrossRefGoogle Scholar
  9. 9.
    Stein C, Hille A, Seidel J, Rijnbout S, Waheed A, Schmidt B, Geuze H, von Figura K (1989) Cloning and expression of human steroid-sulfatase. J Biol Chem 264:13865–13872PubMedGoogle Scholar
  10. 10.
    Helenius A, Aebi M (2001) Intracellular functions of N-linked glycans. Science 291:2364–2369PubMedCrossRefGoogle Scholar
  11. 11.
    Helenius A (1994) How N-linked oligosaccharides affect glycoprotein folding in the endoplasmic reticulum. Mol Biol Cell 5:253–265PubMedGoogle Scholar
  12. 12.
    Kornfeld S (1998) Diseases of abnormal protein glycosylation: an emerging area. J Clin Invest 101:1293–1295PubMedCrossRefGoogle Scholar
  13. 13.
    Millat G, Froissart R, Maire I, Bozon D (1997) IDS transfer from overexpressing cells to IDS-deficient cells. Exp Cell Res 230:362–367PubMedCrossRefGoogle Scholar
  14. 14.
    Tikkanen R, Enomaa N, Riikonen A, Ikonen E, Peltonen L (1995) Intracellular sorting of aspartylglucosaminidase: the role of N-linked oligosaccharides and evidence of Man-6-P-independent lysosomal targeting. DNA Cell Biol 14:305–312PubMedCrossRefGoogle Scholar
  15. 15.
    Spiro RG (2004) Role of N-linked polymannose oligosaccharides in targeting glycoproteins for endoplasmic reticulum-associated degradation. Cell Mol Life Sci 61:1025–1041PubMedCrossRefGoogle Scholar
  16. 16.
    Zhu Y, Doray B, Poussu A, Lehto VP, Kornfeld S (2001) Binding of GGA2 to the lysosomal enzyme sorting motif of the mannose 6-phosphate receptor. Science 292:1716–1718PubMedCrossRefGoogle Scholar
  17. 17.
    Doray B, Ghosh P, Griffith J, Geuze HJ, Kornfeld S (2002) Cooperation of GGAs and AP-1 in packaging MPRs at the trans-Golgi network. Science 297:1700–1703PubMedCrossRefGoogle Scholar
  18. 18.
    Brown WJ, Farquhar MG (1984) The mannose-6-phosphate receptor for lysosomal enzymes is concentrated in cis Golgi cisternae. Cell 36:295–307PubMedCrossRefGoogle Scholar
  19. 19.
    Brown WJ, Farquhar MG (1987) The distribution of 215-kilodalton mannose 6-phosphate receptors within cis (heavy) and trans (light) Golgi subfractions varies in different cell types. Proc Natl Acad Sci USA 84:9001–9005PubMedCrossRefGoogle Scholar
  20. 20.
    Sahagian GG, Neufeld EF (1983) Biosynthesis and turnover of the mannose 6-phosphate receptor in cultured Chinese hamster ovary cells. J Biol Chem 258:7121–7128PubMedGoogle Scholar
  21. 21.
    Koster A, Saftig P, Matzner U, von Figura K, Peters C, Pohlmann R (1993) Targeted disruption of the M(r) 46,000 mannose 6-phosphate receptor gene in mice results in misrouting of lysosomal proteins. EMBO J 12:5219–5223PubMedGoogle Scholar
  22. 22.
    Gabel CA, Goldberg DE, Kornfeld S (1983) Identification and characterization of cells deficient in the mannose 6-phosphate receptor: evidence for an alternate pathway for lysosomal enzyme targeting. Proc Natl Acad Sci USA 80:775–779PubMedCrossRefGoogle Scholar
  23. 23.
    Nolan CM, Creek KE, Grubb JH, Sly WS (1987) Antibody to the phosphomannosyl receptor inhibits recycling of receptor in fibroblasts. J Cell Biochem 35:137–151PubMedCrossRefGoogle Scholar
  24. 24.
    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 6:2677–2681PubMedGoogle Scholar
  25. 25.
    Dahms NM, Lobel P, Kornfeld S (1989) Mannose 6-phosphate receptors and lysosomal enzyme targeting. J Biol Chem 264:12115–12118PubMedGoogle Scholar
  26. 26.
    Abeijon C, Mandon EC, Hirschberg CB (1997) Transporters of nucleotide sugars, nucleotide sulfate and ATP in the Golgi apparatus. Trends Biochem Sci 22:203–207PubMedCrossRefGoogle Scholar
  27. 27.
    Honke K, Taniguchi N (2002) Sulfotransferases and sulfated oligosaccharides. Med Res Rev 22:637–654PubMedCrossRefGoogle Scholar
  28. 28.
    Habuchi H, Habuchi O, Kimata K (2004) Sulfation pattern in glycosaminoglycan: does it have a code? Glycoconj J 21:47–52PubMedCrossRefGoogle Scholar
  29. 29.
    Esko JD, Lindahl U (2001) Molecular diversity of heparan sulfate. J Clin Invest 108:169–173PubMedGoogle Scholar
  30. 30.
    Esko JD, Selleck SB (2002) Order out of chaos: assembly of ligand binding sites in heparan sulfate. Annu Rev Biochem 71:435–471PubMedCrossRefGoogle Scholar
  31. 31.
    Binari RC, Staveley BE, Johnson WA, Godavarti R, Sasisekharan R, Manoukian AS (1997) Genetic evidence that heparin-like glycosaminoglycans are involved in wingless signaling. Development 124:2623–2632PubMedGoogle Scholar
  32. 32.
    Haerry TE, Heslip TR, Marsh JL, O’Connor MB (1997) Defects in glucuronate biosynthesis disrupt Wingless signaling in Drosophila. Development 124:3055–3064PubMedGoogle Scholar
  33. 33.
    Lin X, Perrimon N (1999) Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling. Nature 400:281–284PubMedCrossRefGoogle Scholar
  34. 34.
    Sen J, Goltz JS, Stevens L, Stein D (1998) Spatially restricted expression of pipe in the Drosophila egg chamber defines embryonic dorsal–ventral polarity. Cell 95:471–481PubMedCrossRefGoogle Scholar
  35. 35.
    Merry CL, Bullock SL, Swan DC, Backen AC, Lyon M, Beddington RS, Wilson VA, Gallagher JT (2001) The molecular phenotype of heparan sulfate in the Hs2st-/- mutant mouse. J Biol Chem 276:35429–35434PubMedCrossRefGoogle Scholar
  36. 36.
    Ai X, Do AT, Lozynska O, Kusche-Gullberg M, Lindahl U, Emerson CP Jr (2003) QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling. J Cell Biol 162:341–351PubMedCrossRefGoogle Scholar
  37. 37.
    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 293:1663–1666PubMedCrossRefGoogle Scholar
  38. 38.
    Wang S, Ai X, Freeman SD, Pownall ME, Lu Q, Kessler DS, Emerson CP Jr (2004) QSulf1, a heparan sulfate 6-O-endosulfatase, inhibits fibroblast growth factor signaling in mesoderm induction and angiogenesis. Proc Natl Acad Sci USA 101:4833–4838PubMedCrossRefGoogle Scholar
  39. 39.
    Viviano BL, Paine-Saunders S, Gasiunas N, Gallagher J, Saunders S (2004) Domain-specific modification of heparan sulfate by Qsulf1 modulates the binding of the bone morphogenetic protein antagonist Noggin. J Biol Chem 279:5604–5611PubMedCrossRefGoogle Scholar
  40. 40.
    Ai X, Do AT, Kusche-Gullberg M, Lindahl U, Lu K, Emerson CP Jr (2006) Substrate specificity and domain functions of extracellular heparan sulfate 6-O-endosulfatases, QSulf1 and QSulf2. J Biol Chem 281:4969–4976PubMedCrossRefGoogle Scholar
  41. 41.
    Lamanna WC, Frese MA, Balleininger M, Dierks T (2008) Sulf loss influences N-, 2-O-, and 6-O-sulfation of multiple heparan sulfate proteoglycans and modulates fibroblast growth factor signaling. J Biol Chem 283:27724–27735PubMedCrossRefGoogle Scholar
  42. 42.
    Morimoto-Tomita M, Uchimura K, Werb Z, Hemmerich S, Rosen SD (2002) Cloning and characterization of two extracellular heparin-degrading endosulfatase in mice and humans. J Biol Chem 277:49175–49185PubMedCrossRefGoogle Scholar
  43. 43.
    Lamanna WC, Baldwin RJ, Padva M, Kalus I, Ten Dam G, van Kuppevelt TH, Gallagher JT, von Figura K, Dierks T, Merry CL (2006) Heparan sulfate 6-O-endosulfatases: discrete in vivo activities and functional co-operativity. Biochem J 400:63–73PubMedCrossRefGoogle Scholar
  44. 44.
    Lamanna WC, Kalus I, Padva M, Baldwin RJ, Merry CL, Dierks T (2007) The heparanome—the enigma of encoding and decoding heparan sulfate sulfation. J Biotechnol 129:290–307PubMedCrossRefGoogle Scholar
  45. 45.
    Langsdorf A, Do AT, Kusche-Gullberg M, Emerson CP Jr, Ai X (2007) Sulfs are regulators of growth factor signaling for satellite cell differentiation and muscle regeneration. Dev Biol 311:464–477PubMedCrossRefGoogle Scholar
  46. 46.
    Dai Y, Yang Y, MacLeod V, Yue X, Rapraeger AC, Shriver Z, Venkataraman G, Sasisekharan R, Sanderson RD (2005) HSulf-1 and HSulf-2 are potent inhibitors of myeloma tumor growth in vivo. J Biol Chem 280:40066–40073PubMedCrossRefGoogle Scholar
  47. 47.
    Holst CR, Bou-Reslan H, Gore BB, Wong K, Grant D, Chalasani S, Carano RA, Frantz GD, Tessier-Lavigne M, Bolon B, French DM, Ashkenazi A (2007) Secreted sulfatases Sulf1 and Sulf2 have overlapping yet essential roles in mouse neonatal survival. PLoS ONE 2:e575PubMedCrossRefGoogle Scholar
  48. 48.
    Ratzka A, Kalus I, Moser M, Dierks T, Mundlos S, Vortkamp A (2008) Redundant function of the heparan sulfate 6-O-endosulfatases Sulf1 and Sulf2 during skeletal development. Dev Dyn 237:339–353PubMedCrossRefGoogle Scholar
  49. 49.
    Ghosh D (2007) Human sulfatases: a structural perspective to catalysis. Cell Mol Life Sci 64:2013–2022PubMedCrossRefGoogle Scholar
  50. 50.
    Jatzkewitz H, Mehl E (1969) Cerebroside-sulphatase and arylsulphatase A deficiency in metachromatic leukodystrophy (ML). J Neurochem 16:19–28PubMedCrossRefGoogle Scholar
  51. 51.
    Mehl E, Jatzkewitz H (1968) Cerebroside 3-sulfate as a physiological substrate of arylsulfatase A. Biochim Biophys Acta 151:619–627PubMedGoogle Scholar
  52. 52.
    Roy AB (1975) l-ascorbic acid 2-sulphate. A substrate for mammalian arylsulphatases. Biochim Biophys Acta 377:356–363PubMedGoogle Scholar
  53. 53.
    Farooqui AA, Mandel P (1977) Recent developments in the biochemistry of globoid and metachromatic leucodystrophies. Biomedicine 26:232–236PubMedGoogle Scholar
  54. 54.
    Fluharty AL, Stevens RL, Goldstein EB, Kihara H (1979) The activity of arylsulfatase A and B on tyrosine O-sulfates. Biochim Biophys Acta 566:321–326PubMedGoogle Scholar
  55. 55.
    Louis AI, Fluharty AL (1991) Activator-dependent hydrolysis of myelin cerebroside sulfate by arylsulfatase A. Dev Neurosci 13:41–46PubMedCrossRefGoogle Scholar
  56. 56.
    Tantibhedhyangkul J, Weerachatyanukul W, Carmona E, Xu H, Anupriwan A, Michaud D, Tanphaichitr N (2002) Role of sperm surface arylsulfatase A in mouse sperm–zona pellucida binding. Biol Reprod 67:212–219PubMedCrossRefGoogle Scholar
  57. 57.
    Matalon R, Arbogast B, Dorfman A (1974) Deficiency of chondroitin sulfate N-acetylgalactosamine 4-sulfate sulfatase in Maroteaux-Lamy syndrome. Biochem Biophys Res Commun 61:1450–1457PubMedCrossRefGoogle Scholar
  58. 58.
    Matalon R, Arbogast B, Justice P, Brandt IK, Dorfman A (1974) Morquio’s syndrome: deficiency of a chondroitin sulfate N-acetylhexosamine sulfate sulfatase. Biochem Biophys Res Commun 61:759–765PubMedCrossRefGoogle Scholar
  59. 59.
    O’Brien JF, Cantz M, Spranger J (1974) Maroteaux-Lamy disease (mucopolysaccharidosis VI), subtype A: deficiency of a N-acetylgalactosamine-4-sulfatase. Biochem Biophys Res Commun 60:1170–1177PubMedCrossRefGoogle Scholar
  60. 60.
    Anson DS, Bielicki J (1999) Sulphamidase. Int J Biochem Cell Biol 31:363–367PubMedCrossRefGoogle Scholar
  61. 61.
    Bielicki J, Hopwood JJ (1991) Human liver N-acetylgalactosamine 6-sulphatase. Purification and characterization. Biochem J 279:515–520PubMedGoogle Scholar
  62. 62.
    Bielicki J, Fuller M, Guo XH, Morris CP, Hopewood JJ, Anson DS (1995) Expression, purification and characterization of recombinant human N-acetylgalactosamine-6-sulphatase. Biochem J 311:333–339PubMedGoogle Scholar
  63. 63.
    Litjens T, Bielicki J, Anson DS, Friderici K, Jones MZ, Hopwood JJ (1997) Expression, purification and characterization of recombinant caprine N-acetylglucosamine-6-sulphatase. Biochem J 327:89–94PubMedGoogle Scholar
  64. 64.
    Gibson GJ, Saccone GT, Brooks DA, Clements PR, Hopwood JJ (1987) Human N-acetylgalactosamine-4-sulphate sulphatase. Purification, monoclonal antibody production and native and subunit Mr values. Biochem J 248:755–764PubMedGoogle Scholar
  65. 65.
    Ginsberg LC, Di Ferrante DT, Di Ferrante N (1978) A substrate for direct measurement of l-iduronic acid 2-sulfate sulfatase. Carbohydr Res 64:225–235PubMedCrossRefGoogle Scholar
  66. 66.
    Neufeld EFM (1999) The metabolic and molecular bases of inherited disease. McGraw-Hill, New YorkGoogle Scholar
  67. 67.
    Settembre C, Fraldi A, Jahreiss L, Spampanato C, Venturi C, Medina D, de Pablo R, Tacchetti C, Rubinsztein DC, Ballabio A (2008) A block of autophagy in lysosomal storage disorders. Hum Mol Genet 17:119–129PubMedCrossRefGoogle Scholar
  68. 68.
    Pacheco CD, Kunkel R, Lieberman AP (2007) Autophagy in Niemann-Pick C disease is dependent upon Beclin-1 and responsive to lipid trafficking defects. Hum Mol Genet 16:1495–1503PubMedCrossRefGoogle Scholar
  69. 69.
    Bidere N, Lorenzo HK, Carmona S, Laforge M, Harper F, Dumont C, Senik A (2003) Cathepsin D triggers Bax activation, resulting in selective apoptosis-inducing factor (AIF) relocation in T lymphocytes entering the early commitment phase to apoptosis. J Biol Chem 278:31401–31411PubMedCrossRefGoogle Scholar
  70. 70.
    Erdal H, Berndtsson M, Castro J, Brunk U, Shoshan MC, Linder S (2005) Induction of lysosomal membrane permeabilization by compounds that activate p53-independent apoptosis. Proc Natl Acad Sci USA 102:192–197PubMedCrossRefGoogle Scholar
  71. 71.
    Tanaka K, Abe M, Sato Y (1999) Roles of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase in the signal transduction of basic fibroblast growth factor in endothelial cells during angiogenesis. Jpn J Cancer Res 90:647–654PubMedGoogle Scholar
  72. 72.
    Reed MJ, Purohit A, Woo LW, Newman SP, Potter BV (2005) Steroid sulfatase: molecular biology, regulation, and inhibition. Endocr Rev 26:171–202PubMedCrossRefGoogle Scholar
  73. 73.
    Suzuki T, Nakata T, Miki Y, Kaneko C, Moriya T, Ishida T, Akinaga S, Hirakawa H, Kimura M, Sasano H (2003) Estrogen sulfotransferase and steroid sulfatase in human breast carcinoma. Cancer Res 63:2762–2770PubMedGoogle Scholar
  74. 74.
    Pasqualini JR, Gelly C, Nguyen BL, Vella C (1989) Importance of estrogen sulfates in breast cancer. J Steroid Biochem 34:155–163PubMedCrossRefGoogle Scholar
  75. 75.
    Ballabio A, Parenti G, Tippett P, Mondello C, Di Maio S, Tenore A, Andria G (1986) X-linked ichthyosis due to steroid sulphatase deficiency associated with Kallmann syndrome (hypogonadotropic hypogonadism and anosmia): linkage relationships with Xg and cloned DNA sequences from the distal short arm of the X chromosome. Hum Genet 72:237–240PubMedCrossRefGoogle Scholar
  76. 76.
    Richard G (2004) Molecular genetics of the ichthyoses. Am J Med Genet C Semin Med Genet 131C:32–44PubMedCrossRefGoogle Scholar
  77. 77.
    Franco B, Meroni G, Parenti G, Levilliers J, Bernard L, Gebbia M, Cox L, Maroteaux P, Sheffield L, Rappold GA, Andria G, Petit C, Ballabio A (1995) A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia punctata (CDPX) and implications for warfarin embryopathy. Cell 81:15–25PubMedCrossRefGoogle Scholar
  78. 78.
    Dierks T, Schmidt B, Borissenko LV, Peng J, Preusser A, Mariappan M, von Figura K (2003) Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C(alpha)-formylglycine generating enzyme. Cell 113:435–444PubMedCrossRefGoogle Scholar
  79. 79.
    Cosma MP, Pepe S, Annunziata I, Newbold RF, Grompe M, Parenti G, Ballabio A (2003) The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases. Cell 113:445–456PubMedCrossRefGoogle Scholar
  80. 80.
    Dierks T, Dickmanns A, Preusser-Kunze A, Schmidt B, Mariappan M, von Figura K, Ficner R, Rudolph MG (2005) Molecular basis for multiple sulfatase deficiency and mechanism for formylglycine generation of the human formylglycine-generating enzyme. Cell 121:541–552PubMedCrossRefGoogle Scholar
  81. 81.
    Preusser-Kunze A, Mariappan M, Schmidt B, Gande SL, Mutenda K, Wenzel D, von Figura K, Dierks T (2005) Molecular characterization of the human Calpha-formylglycine-generating enzyme. J Biol Chem 280:14900–14910PubMedCrossRefGoogle Scholar
  82. 82.
    Zito E, Buono M, Pepe S, Settembre C, Annunziata I, Surace EM, Dierks T, Monti M, Cozzolino M, Pucci P, Ballabio A, Cosma MP (2007) Sulfatase modifying factor 1 trafficking through the cells: from endoplasmic reticulum to the endoplasmic reticulum. EMBO J 26:2443–2453PubMedCrossRefGoogle Scholar
  83. 83.
    Fraldi A, Zito E, Annunziata F, Lombardi A, Cozzolino M, Monti M, Spampanato C, Ballabio A, Pucci P, Sitia R, Cosma MP (2008) Multistep, sequential control of the trafficking and function of the multiple sulfatase deficiency gene product, SUMF1 by PDI, ERGIC-53 and ERp44. Hum Mol Genet 17:2610–2621PubMedCrossRefGoogle Scholar
  84. 84.
    Tsai B, Rodighiero C, Lencer WI, Rapoport TA (2001) Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin. Cell 104:937–948PubMedCrossRefGoogle Scholar
  85. 85.
    Appenzeller C, Andersson H, Kappeler F, Hauri HP (1999) The lectin ERGIC-53 is a cargo transport receptor for glycoproteins. Nat Cell Biol 1:330–334PubMedCrossRefGoogle Scholar
  86. 86.
    Appenzeller-Herzog C, Roche AC, Nufer O, Hauri HP (2004) pH-induced conversion of the transport lectin ERGIC-53 triggers glycoprotein release. J Biol Chem 279:12943–12950PubMedCrossRefGoogle Scholar
  87. 87.
    Anelli T, Alessio M, Mezghrani A, Simmen T, Talamo F, Bachi A, Sitia R (2002) ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. EMBO J 21:835–844PubMedCrossRefGoogle Scholar
  88. 88.
    Gilchrist A, Au CE, Hiding J, Bell AW, Fernandez-Rodriguez J, Lesimple S, Nagaya H, Roy L, Gosline SJ, Hallett M, Paiement J, Kearney RE, Nilsson T, Bergeron JJ (2006) Quantitative proteomics analysis of the secretory pathway. Cell 127:1265–1281PubMedCrossRefGoogle Scholar
  89. 89.
    Anelli T, Ceppi S, Bergamelli L, Cortini M, Masciarelli S, Valetti C, Sitia R (2007) Sequential steps and checkpoints in the early exocytic compartment during secretory IgM biogenesis. EMBO J 26:4177–4188PubMedCrossRefGoogle Scholar
  90. 90.
    Anelli T, Alessio M, Bachi A, Bergamelli L, Bertoli G, Camerini S, Mezghrani A, Ruffato E, Simmen T, Sitia R (2003) Thiol-mediated protein retention in the endoplasmic reticulum: the role of ERp44. EMBO J 22:5015–5022PubMedCrossRefGoogle Scholar
  91. 91.
    Mariappan M, Radhakrishnan K, Dierks T, Schmidt B, von Figura K (2008) ERp44 mediates a thiol-independent retention of formylglycine-generating enzyme in the endoplasmic reticulum. J Biol Chem 283:6375–6383PubMedCrossRefGoogle Scholar
  92. 92.
    Settembre C, Annunziata I, Spampanato C, Zarcone D, Cobellis G, Nusco E, Zito E, Tacchetti C, Cosma MP, Ballabio A (2007) Systemic inflammation and neurodegeneration in a mouse model of multiple sulfatase deficiency. Proc Natl Acad Sci USA 104:4506–4511PubMedCrossRefGoogle Scholar
  93. 93.
    Settembre C, Arteaga-Solis E, McKee MD, de Pablo R, Al Awqati Q, Ballabio A, Karsenty G (2008) Proteoglycan desulfation determines the efficiency of chondrocyte autophagy and the extent of FGF signaling during endochondral ossification. Genes Dev 22:2645–2650PubMedCrossRefGoogle Scholar
  94. 94.
    Cardone M, Polito VA, Pepe S, Mann L, D’Azzo A, Auricchio A, Ballabio A, Cosma MP (2006) Correction of Hunter syndrome in the MPSII mouse model by AAV2/8-mediated gene delivery. Hum Mol Genet 15:1225–1236PubMedCrossRefGoogle Scholar
  95. 95.
    Polito VA, Cosma MP (2009) IDS crossing of the blood–brain barrier corrects CNS defects in MPSII mice. Am J Hum Genet 85:296–301PubMedCrossRefGoogle Scholar
  96. 96.
    Tessitore A, Faella A, O’Malley T, Cotugno G, Doria M, Kunieda T, Matarese G, Haskins M, Auricchio A (2008) Biochemical, pathological, and skeletal improvement of mucopolysaccharidosis VI after gene transfer to liver but not to muscle. Mol Ther 16:30–37PubMedCrossRefGoogle Scholar
  97. 97.
    Biffi A, De Palma M, Quattrini A, Del Carro U, Amadio S, Visigalli I, Sessa M, Fasano S, Brambilla R, Marchesini S, Bordignon C, Naldini L (2004) Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells. J Clin Invest 113:1118–1129PubMedGoogle Scholar
  98. 98.
    Fraldi A, Biffi A, Lombardi A, Visigalli I, Pepe S, Settembre C, Nusco E, Auricchio A, Naldini L, Ballabio A, Cosma MP (2007) SUMF1 enhances sulfatase activities in vivo in five sulfatase deficiencies. Biochem J 405:305–312Google Scholar
  99. 99.
    Fraldi A, Hemsley K, Crawley A, Lombardi A, Lau A, Sutherland L, Auricchio A, Ballabio A, Hopwood JJ (2007) Functional correction of CNS lesions in an MPS-IIIA mouse model by intracerebral AAV-mediated delivery of sulfamidase and SUMF1 genes. Hum Mol Genet 16:2693–2702PubMedCrossRefGoogle Scholar
  100. 100.
    Freiberg RA, Choate KA, Deng H, Alperin ES, Shapiro LJ, Khavari PA (1997) A model of corrective gene transfer in X-linked ichthyosis. Hum Mol Genet 6:927–933PubMedCrossRefGoogle Scholar
  101. 101.
    Hernandez-Guzman FG, Higashiyama T, Pangborn W, Osawa Y, Ghosh D (2003) Structure of human estrone sulfatase suggests functional roles of membrane association. J Biol Chem 278:22989–22997PubMedCrossRefGoogle Scholar
  102. 102.
    Bond CS, Clements PR, Ashby SJ, Collyer CA, Harrop SJ, Hopwood JJ, Guss JM (1997) Structure of a human lysosomal sulfatase. Structure 5:277–289PubMedCrossRefGoogle Scholar

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© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  1. 1.Telethon Institute of Genetics and Medicine (TIGEM), CNRNaplesItaly
  2. 2.Institute of Genetics and Biophysics (IGB), CNRNaplesItaly

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