Drosophila Heparan Sulfate 6-O-Endosulfatase Sulf1 Facilitates Wingless (Wg) Protein Degradation

• DOI: 10.1074/jbc.m112.447029
• Publication Date: 2013-01-09T13:55:45Z
• Authors: Adam Kleinschmit; Masahiko Takemura; Katsufumi Dejima; Pui Yee Choi; Hiroshi Nakato
• Keywords: Perlecan

Heparan sulfate proteoglycans regulate various physiological and developmental processes through interactions with a number of protein ligands. (HS)-ligand binding depends on the amount patterns groups HS, which are controlled by HS sulfotransferases in Golgi apparatus as well extracellular 6-O-endosulfatases called "Sulfs." Sulfs family secreted molecules that specifically remove 6-O-sulfate within highly sulfated regions HS. Vertebrate promote Wnt signaling, whereas only Drosophila homologue Sulfs, Sulf1, negatively regulates Wingless (Wg) signaling. To understand molecular mechanism for negative regulation Wg signaling we studied effects Sulf1 HS-Wg interaction stability. overexpression strongly inhibited to Dally, potential target heparan proteoglycan Sulf1. This effect is similar vertebrate Sulfs. Using vitro, vivo, ex vivo systems, show reduces levels, at least partly facilitating degradation. In addition, expression human wing disc lowers levels protein, observed Our study demonstrates have an intrinsically activity function fate Wnt/Wg ligands context-dependent.