title: Two functional domains in C. elegans glypican LON-2 can independently inhibit BMP-like signaling.
abstract: Glypicans are multifunctional proteoglycans with regulatory roles in several intercellular signaling pathways. Here, we examine the functional requirements for glypican regulation of bone morphogenetic protein (BMP)-mediated body length in C. elegans. We provide evidence that two parts of C. elegans glypican LON-2 can independently inhibit BMP signaling in vivo: the N-terminal furin protease product and the C-terminal region containing heparan sulfate attachment sequences. While the C-terminal protease product is dispensable for LON-2 minimal core protein activity, it does affect the localization of LON-2. Cleavage of LON-2 into two parts at the conserved furin protease site is not required for LON-2 to inhibit BMP-like signaling. The glycosyl-phosphatidylinositol (GPI) membrane anchor is also not absolutely required for LON-2 activity. Finally, we show that an RGD protein-protein interaction motif in the LON-2 N-terminal domain is necessary for LON-2 core protein activity, suggesting that LON-2 inhibits BMP signaling by acting as a scaffold for BMP and an RGD-binding protein.
authors.affiliation: Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M Health Science Center, College Station, TX 77843-1114, USA.
authors.forename: Suparna
authors.initials: S
authors.lastname: Taneja-Bageshwar
authors.forename: Tina L
authors.initials: TL
authors.lastname: Gumienny
mesh_terms: D000818:Animals; D049628:Body Size / Q000235:genetics / Q000502:physiology; D001837:Body Weights and Measures; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism* / Q000494:pharmacology; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D053673:Glypicans / Q000378:metabolism* / Q000494:pharmacology; D018613:Microscopy, Confocal; D017434:Protein Structure, Tertiary / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D029742:Caenorhabditis elegans Proteins; D017261:Glycosylphosphatidylinositols; D053673:Glypicans; C518316:LON-2 protein, C elegans