NDLI: The role of Drosophila heparan sulfate 6-O-endosulfatase in sulfation compensation.

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The role of Drosophila heparan sulfate 6-O-endosulfatase in sulfation compensation.

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The role of Drosophila heparan sulfate 6-O-endosulfatase in sulfation compensation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Dejima, Katsufumi Choi, Pui Yee Toyoda, Hidenao Takemura, Masahiko Kinoshita-toyoda, Akiko Kleinschmit, Adam Nakato, Hiroshi
Description	Author Affiliation: Dejima K ( Department of Genetics, University of Minnesota, Minneapolis, Minnesota 55455, USA.)
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, 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.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	9
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Drosophila Proteins Metabolism Sulfatases Sulfotransferases Animals Body Patterning Physiology Genetics Drosophila Melanogaster Fibroblast Growth Factors Signal Transduction Research Support, N.I.H., Extramural Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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