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),pp.6574-82
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