Dejima Katsufumi
   Department   School of Medicine, School of Medicine
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title The role of Drosophila heparan sulfate 6-O-endosulfatase in sulfation compensation.
Journal Formal name:The Journal of biological chemistry
Abbreviation:J Biol Chem
ISSN code:1083-351X(Electronic)0021-9258(Linking)
Volume, Issue, Page 288(9),6574-82頁
Author and coauthor Dejima Katsufumi, Kleinschmit Adam, Takemura Masahiko, Choi Pui Yee, Kinoshita-Toyoda Akiko, Toyoda Hidenao, Nakato Hiroshi
Publication date 2013/03
Summary 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, extracellular HS 6-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.
DOI 10.1074/jbc.M112.404830
Document No. 23339195