title: The TGF-β co-receptor, CD109, promotes internalization and degradation of TGF-β receptors.
abstract: Transforming growth factor-β (TGF-β) is implicated in numerous pathological disorders, including cancer and mediates a broad range of biological responses by signaling through the type I and II TGF-β receptors. Internalization of these receptors via the clathrin-coated pits pathway facilitates SMAD-mediated signaling, whereas internalization via the caveolae pathway is associated with receptor degradation. Thus, molecules that modulate receptor endocytosis are likely to play a critical role in regulating TGF-β action. We previously identified CD109, a GPI-anchored protein, as a TGF-β co-receptor and a negative regulator of TGF-β signaling. Here, we demonstrate that CD109 associates with caveolin-1, a major component of the caveolae. Moreover, CD109 increases binding of TGF-β to its receptors and enhances their internalization via the caveolae. In addition, CD109 promotes localization of the TGF-β receptors into the caveolar compartment in the presence of ligand and facilitates TGF-β-receptor degradation. Thus, CD109 regulates TGF-β receptor endocytosis and degradation to inhibit TGF-β signaling. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
authors.affiliation: Division of Plastic Surgery, Department of Surgery, McGill University, Montreal, QC, Canada.
authors.forename: Albane A
authors.initials: AA
authors.lastname: Bizet
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tran-Khanh
authors.forename: Anshuman
authors.initials: A
authors.lastname: Saksena
authors.forename: Joshua
authors.initials: J
authors.lastname: Vorstenbosch
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Finnson
authors.forename: Michael D
authors.initials: MD
authors.lastname: Buschmann
authors.forename: Anie
authors.initials: A
authors.lastname: Philip
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D002451:Cell Compartmentation; D002460:Cell Line; D004705:Endocytosis; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C120523:CD109 protein, human; D051242:Caveolin 1; D058851:GPI-Linked Proteins; D008024:Ligands; D009363:Neoplasm Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D046988:Proteasome Endopeptidase Complex