title: Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells.
abstract: The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology.
authors.affiliation: Center for Systems Biology, Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xia
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Babitt
authors.forename: Richard
authors.initials: R
authors.lastname: Bouley
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nicolas
authors.initials: N
authors.lastname: Da Silva
authors.forename: Shanzhuo
authors.initials: S
authors.lastname: Chen
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Samad
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Brenner
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Anderson
authors.forename: Charles C
authors.initials: CC
authors.lastname: Hong
authors.forename: Alan L
authors.initials: AL
authors.lastname: Schneyer
authors.forename: Dennis
authors.initials: D
authors.lastname: Brown
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Lin
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology*; D007668:Kidney; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules / Q000502:physiology*; D015398:Signal Transduction; D019459:Urothelium / Q000166:cytology
chemical_list: D019485:Bone Morphogenetic Proteins; C484269:DRAGON protein, mouse; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules