The Role of Drosophila Heparan Sulfate 6-O-Endosulfatase in Sulfation Compensation.

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Title: The Role of Drosophila Heparan Sulfate 6-O-Endosulfatase in Sulfation Compensation.
Authors: Dejima, Katsufumi1, Kleinschmit, Adam1, Takemura, Masahiko1, Pui Yee Choi1, Kinoshita-Toyoda, Akiko2, Toyoda, Hidenao2, Nakato, Hiroshi1 nakat003@umn.edu
Source: Journal of Biological Chemistry. 3/1/2013, Vol. 288 Issue 9, p6574-6582. 9p.
Subjects: Drosophila, Heparan sulfate proteoglycans, Biosynthesis, Sulfation, Proteoglycans, Decapentaplegic protein, Hedgehog signaling proteins
Abstract: The biosynthesis of heparan sulfate proteoglycans is tightly regulated by multiple feedback mechanisms, which support robust developmental systems. One of the regulatory network systems controlling heparan sulfate (HS) biosynthesis is sulfation compensation. A previous study using Drosophila HS 2-O- and 6-O-sulfotransferase (Hs2st and Hs6st) mutants showed that loss of sulfation at one position is compensated by increased sulfation at other positions, supporting normal FGF signaling. Here, we show that HS sulfation compensation rescues both Decapentaplegic and Wingless signaling, suggesting a universal role of this regulatory system in multiple pathways in Drosophila. Furthermore, we identified Sulf1, extracellularHS6-O-endosulfatase, as a novel component of HS sulfation compensation. Simultaneous loss of Hs2st and Sulf1 led to 6-O-oversulfation, leading to patterning defects, overgrowth, and lethality. These phenotypes are caused at least partly by abnormal up-regulation of Hedgehog signaling. Thus, sulfation compensation depends on the coordinated activities of Hs2st, Hs6st, and Sulf1. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
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  Data: The Role of Drosophila Heparan Sulfate 6-O-Endosulfatase in Sulfation Compensation.
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  Data: <searchLink fieldCode="AR" term="%22Dejima%2C+Katsufumi%22">Dejima, Katsufumi</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Kleinschmit%2C+Adam%22">Kleinschmit, Adam</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Takemura%2C+Masahiko%22">Takemura, Masahiko</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Pui+Yee+Choi%22">Pui Yee Choi</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Kinoshita-Toyoda%2C+Akiko%22">Kinoshita-Toyoda, Akiko</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Toyoda%2C+Hidenao%22">Toyoda, Hidenao</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Nakato%2C+Hiroshi%22">Nakato, Hiroshi</searchLink><relatesTo>1</relatesTo><i> nakat003@umn.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 3/1/2013, Vol. 288 Issue 9, p6574-6582. 9p.
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  Data: <searchLink fieldCode="DE" term="%22Drosophila%22">Drosophila</searchLink><br /><searchLink fieldCode="DE" term="%22Heparan+sulfate+proteoglycans%22">Heparan sulfate proteoglycans</searchLink><br /><searchLink fieldCode="DE" term="%22Biosynthesis%22">Biosynthesis</searchLink><br /><searchLink fieldCode="DE" term="%22Sulfation%22">Sulfation</searchLink><br /><searchLink fieldCode="DE" term="%22Proteoglycans%22">Proteoglycans</searchLink><br /><searchLink fieldCode="DE" term="%22Decapentaplegic+protein%22">Decapentaplegic protein</searchLink><br /><searchLink fieldCode="DE" term="%22Hedgehog+signaling+proteins%22">Hedgehog signaling proteins</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: The biosynthesis of heparan sulfate proteoglycans is tightly regulated by multiple feedback mechanisms, which support robust developmental systems. One of the regulatory network systems controlling heparan sulfate (HS) biosynthesis is sulfation compensation. A previous study using Drosophila HS 2-O- and 6-O-sulfotransferase (Hs2st and Hs6st) mutants showed that loss of sulfation at one position is compensated by increased sulfation at other positions, supporting normal FGF signaling. Here, we show that HS sulfation compensation rescues both Decapentaplegic and Wingless signaling, suggesting a universal role of this regulatory system in multiple pathways in Drosophila. Furthermore, we identified Sulf1, extracellularHS6-O-endosulfatase, as a novel component of HS sulfation compensation. Simultaneous loss of Hs2st and Sulf1 led to 6-O-oversulfation, leading to patterning defects, overgrowth, and lethality. These phenotypes are caused at least partly by abnormal up-regulation of Hedgehog signaling. Thus, sulfation compensation depends on the coordinated activities of Hs2st, Hs6st, and Sulf1. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1074/jbc.M112.404830
    Languages:
      – Code: eng
        Text: English
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        PageCount: 9
        StartPage: 6574
    Subjects:
      – SubjectFull: Drosophila
        Type: general
      – SubjectFull: Heparan sulfate proteoglycans
        Type: general
      – SubjectFull: Biosynthesis
        Type: general
      – SubjectFull: Sulfation
        Type: general
      – SubjectFull: Proteoglycans
        Type: general
      – SubjectFull: Decapentaplegic protein
        Type: general
      – SubjectFull: Hedgehog signaling proteins
        Type: general
    Titles:
      – TitleFull: The Role of Drosophila Heparan Sulfate 6-O-Endosulfatase in Sulfation Compensation.
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            NameFull: Dejima, Katsufumi
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            NameFull: Kleinschmit, Adam
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            NameFull: Takemura, Masahiko
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            NameFull: Pui Yee Choi
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            NameFull: Kinoshita-Toyoda, Akiko
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            NameFull: Toyoda, Hidenao
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            NameFull: Nakato, Hiroshi
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            – D: 01
              M: 03
              Text: 3/1/2013
              Type: published
              Y: 2013
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            – TitleFull: Journal of Biological Chemistry
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