The RGM protein DRAG-1 positively regulates a BMP-like signaling pathway in Caenorhabditis elegans

Development. 2010 Jul;137(14):2375-84. doi: 10.1242/dev.051615. Epub 2010 Jun 9.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Bone Morphogenetic Proteins / physiology*
  • Caenorhabditis elegans* / genetics
  • Caenorhabditis elegans* / growth & development
  • Caenorhabditis elegans* / metabolism
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mutation
  • Neurons / metabolism
  • Protein Binding / genetics
  • Proteins / genetics
  • Proteins / metabolism
  • Signal Transduction / genetics*

Substances

  • Bone Morphogenetic Proteins
  • Membrane Proteins
  • Proteins