Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells.
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.
Xia
Yin
Y
Center for Systems Biology, Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Babitt
Jodie L
JL
Bouley
Richard
R
Zhang
Ying
Y
Da Silva
Nicolas
N
Chen
Shanzhuo
S
Zhuang
Zhenjie
Z
Samad
Tarek A
TA
Brenner
Gary J
GJ
Anderson
Jennifer L
JL
Hong
Charles C
CC
Schneyer
Alan L
AL
Brown
Dennis
D
Lin
Herbert Y
HY
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
D019485:Bone Morphogenetic Proteins; C484269:DRAGON protein, mouse; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules