title: The role of Drosophila heparan sulfate 6-O-endosulfatase in sulfation compensation.
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.
authors: Department of Genetics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors: Katsufumi
authors: K
authors: Dejima
authors: Adam
authors: A
authors: Kleinschmit
authors: Masahiko
authors: M
authors: Takemura
authors: Pui Yee
authors: PY
authors: Choi
authors: Akiko
authors: A
authors: Kinoshita-Toyoda
authors: Hidenao
authors: H
authors: Toyoda
authors: Hiroshi
authors: H
authors: Nakato
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013429:Sulfatases / Q000235:genetics / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D005346:Fibroblast Growth Factors; D015238:Sulfotransferases; C404189:heparan sulfate 6-O-sulfotransferase; C106358:heparan-sulfate 2-sulfotransferase; C568065:SULF1 protein, Drosophila; D013429:Sulfatases