RRC ID 3578
著者 Gumienny TL, MacNeil LT, Wang H, de Bono M, Wrana JL, Padgett RW.
タイトル Glypican LON-2 is a conserved negative regulator of BMP-like signaling in Caenorhabditis elegans.
ジャーナル Curr Biol
Abstract Bone morphogenetic protein (BMP) pathways are required for a wide variety of developmental and homeostatic decisions, and mutations in signaling components are associated with several diseases. An important aspect of BMP control is the extracellular regulation of these pathways. We show that LON-2 negatively regulates a BMP-like signaling pathway that controls body length in C. elegans. lon-2 acts genetically upstream of the BMP-like gene dbl-1, and loss of lon-2 function results in animals that are longer than normal. LON-2 is a conserved member of the glypican family of heparan sulfate proteoglycans, a family with several members known to regulate growth-factor signaling in many organisms. LON-2 is functionally conserved because the Drosophila glypican gene dally rescues the lon-2(lf) body-size defect. We show that the LON-2 protein binds BMP2 in vitro, and a mutant variation of LON-2 found in lon-2(e2140) animals diminishes this interaction. We propose that LON-2 binding to DBL-1 negatively regulates this pathway in C. elegans by attenuating ligand-receptor interactions. This is the first report of a glypican directly interacting with a growth-factor pathway in C. elegans and provides a mechanistic model for glypican regulation of growth-factor pathways.
巻・号 17(2)
ページ 159-64
公開日 2007-1-23
DOI 10.1016/j.cub.2006.11.065
PII S0960-9822(06)02585-1
PMID 17240342
MeSH Animals Bone Morphogenetic Proteins / metabolism Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* Drosophila Proteins / genetics Glypicans / genetics Glypicans / metabolism Glypicans / physiology* Membrane Glycoproteins / genetics Neuropeptides / metabolism Proteoglycans / genetics Signal Transduction / physiology* Subcutaneous Tissue / growth & development Transforming Growth Factor beta / metabolism
IF 9.601
引用数 56
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
線虫 tm472