The RGM protein DRAG-1 positively regulates a BMP-like signaling pathway in Caenorhabditis elegans.
The bone morphogenetic protein (BMP) signaling pathway regulates multiple developmental and homeostatic processes. Mutations in the pathway can cause a variety of somatic and hereditary disorders in humans. Multiple levels of regulation, including extracellular regulation, ensure proper spatiotemporal control of BMP signaling in the right cellular context. We have identified a modulator of the BMP-like Sma/Mab pathway in C. elegans called DRAG-1. DRAG-1 is the sole member of the repulsive guidance molecule (RGM) family of proteins in C. elegans, and is crucial in regulating body size and mesoderm development. Using a combination of molecular genetic and biochemical analyses, we demonstrate that DRAG-1 is a membrane-associated protein that functions at the ligand-receptor level to modulate the Sma/Mab pathway in a cell-type-specific manner. We further show that DRAG-1 positively modulates this BMP-like pathway by using a novel Sma/Mab-responsive reporter. Our work provides a direct link between RGM proteins and BMP signaling in vivo and a simple and genetically tractable system for mechanistic studies of RGM protein regulation of BMP pathways.
Tian
Chenxi
C
Department of Molecular Biology and Genetics, 439 Biotechnology Building, Cornell University, Ithaca, NY 14853, USA.
Sen
Debjeet
D
Shi
Herong
H
Foehr
Marisa L
ML
Plavskin
Yevgeniy
Y
Vatamaniuk
Olena K
OK
Liu
Jun
J
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
D019485:Bone Morphogenetic Proteins; D008565:Membrane Proteins; D011506:Proteins