TY - JOUR
T1 - The role of drosophila heparan sulfate 6-O-endosulfatase in sulfation compensation
AU - Dejima, Katsufumi
AU - Kleinschmit, Adam
AU - Takemura, Masahiko
AU - Choi, Pui Yee
AU - Kinoshita-Toyoda, Akiko
AU - Toyoda, Hidenao
AU - Nakato, Hiroshi
PY - 2013/3/1
Y1 - 2013/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84874772582&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874772582&partnerID=8YFLogxK
U2 - 10.1074/jbc.M112.404830
DO - 10.1074/jbc.M112.404830
M3 - Article
C2 - 23339195
AN - SCOPUS:84874772582
SN - 0021-9258
VL - 288
SP - 6574
EP - 6582
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 9
ER -