PMID- 19853561 OWN - NLM STAT- MEDLINE DCOM- 20091110 LR - 20211020 IS - 1878-1551 (Electronic) IS - 1534-5807 (Print) IS - 1534-5807 (Linking) VI - 17 IP - 4 DP - 2009 Oct TI - The core protein of glypican Dally-like determines its biphasic activity in wingless morphogen signaling. PG - 470-81 LID - 10.1016/j.devcel.2009.09.001 [doi] AB - Dally-like (Dlp) is a glypican-type heparan sulfate proteoglycan (HSPG), containing a protein core and attached glycosaminoglycan (GAG) chains. In Drosophila wing discs, Dlp represses short-range Wingless (Wg) signaling, but activates long-range Wg signaling. Here, we show that Dlp core protein has similar biphasic activity as wild-type Dlp. Dlp core protein can interact with Wg; the GAG chains enhance this interaction. Importantly, we find that Dlp exhibits a biphasic response, regardless of whether its glycosylphosphatidylinositol linkage to the membrane can be cleaved. Rather, the transition from signaling activator to repressor is determined by the relative expression levels of Dlp and the Wg receptor, Frizzled (Fz) 2. Based on these data, we propose that the principal function of Dlp is to retain Wg on the cell surface. As such, it can either compete with the receptor or provide ligands to the receptor, depending on the ratios of Wg, Fz2, and Dlp. FAU - Yan, Dong AU - Yan D AD - Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. FAU - Wu, Yihui AU - Wu Y FAU - Feng, Ying AU - Feng Y FAU - Lin, Sheng-Cai AU - Lin SC FAU - Lin, Xinhua AU - Lin X LA - eng GR - R01 GM063891/GM/NIGMS NIH HHS/United States GR - R01 GM063891-09/GM/NIGMS NIH HHS/United States GR - 2R01 GM063891/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Dev Cell JT - Developmental cell JID - 101120028 RN - 0 (Drosophila Proteins) RN - 0 (Frizzled Receptors) RN - 0 (Glycosaminoglycans) RN - 0 (Glycosylphosphatidylinositols) RN - 0 (Heparan Sulfate Proteoglycans) RN - 0 (Proteoglycans) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (Wnt1 Protein) RN - 0 (dlp protein, Drosophila) RN - 0 (fz2 protein, Drosophila) RN - 0 (wg protein, Drosophila) RN - EC 1.13.12.- (Luciferases) SB - IM MH - Animals MH - Drosophila Proteins/genetics/*metabolism MH - Drosophila melanogaster MH - Embryo, Nonmammalian/cytology/metabolism MH - Endocytosis MH - Frizzled Receptors/genetics/*metabolism MH - *Gene Expression Regulation, Developmental MH - Glycosaminoglycans/metabolism MH - Glycosylphosphatidylinositols/metabolism MH - Heparan Sulfate Proteoglycans/metabolism MH - Immunoprecipitation MH - Luciferases/metabolism MH - Proteoglycans/genetics/*metabolism MH - Receptors, G-Protein-Coupled/genetics/*metabolism MH - *Signal Transduction MH - Wings, Animal/cytology/metabolism MH - Wnt1 Protein/genetics/*metabolism PMC - PMC3326419 MID - NIHMS365689 EDAT- 2009/10/27 06:00 MHDA- 2009/11/11 06:00 PMCR- 2012/04/15 CRDT- 2009/10/27 06:00 PHST- 2009/01/27 00:00 [received] PHST- 2009/07/14 00:00 [revised] PHST- 2009/09/01 00:00 [accepted] PHST- 2009/10/27 06:00 [entrez] PHST- 2009/10/27 06:00 [pubmed] PHST- 2009/11/11 06:00 [medline] PHST- 2012/04/15 00:00 [pmc-release] AID - S1534-5807(09)00383-9 [pii] AID - 10.1016/j.devcel.2009.09.001 [doi] PST - ppublish SO - Dev Cell. 2009 Oct;17(4):470-81. doi: 10.1016/j.devcel.2009.09.001.