The Bro1-domain protein, EGO-2, promotes Notch signaling in Caenorhabditis elegans

Genetics. 2007 Aug;176(4):2265-77. doi: 10.1534/genetics.107.071225. Epub 2007 Jul 1.

Abstract

In Caenorhabditis elegans, as in other animals, Notch-type signaling mediates numerous inductive events during development. The mechanism of Notch-type signaling involves proteolytic cleavage of the receptor and subsequent transport of the receptor intracellular domain to the nucleus, where it acts as a transcriptional regulator. Notch-type signaling activity is modulated by post-translational modifications and endocytosis of ligand and receptor. We previously identified the ego-2 (enhancer of glp-1) gene as a positive regulator of germline proliferation that interacts genetically with the GLP-1/Notch signaling pathway in the germline. Here, we show that ego-2 positively regulates signaling in various tissues via both GLP-1 and the second C. elegans Notch-type receptor, LIN-12. ego-2 activity also promotes aspects of development not known to require GLP-1 or LIN-12. The EGO-2 protein contains a Bro1 domain, which is known in other systems to localize to certain endosomal compartments. EGO-2 activity in the soma promotes GLP-1 signaling in the germline, consistent with a role for EGO-2 in production of active ligand. Another C. elegans Bro1-domain protein, ALX-1, is known to interact physically with LIN-12/Notch. We document a complex phenotypic interaction between ego-2 and alx-1, consistent with their relationship being antagonistic with respect to some developmental processes and agonistic with respect to others.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Chromosome Mapping
  • DNA, Helminth / genetics
  • Endocytosis
  • Female
  • Genes, Helminth
  • Germ Cells
  • Male
  • Meiosis / genetics
  • Meiosis / physiology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Polymorphism, Single Nucleotide
  • RNA Interference
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Spermatogenesis / genetics
  • Spermatogenesis / physiology

Substances

  • Caenorhabditis elegans Proteins
  • DNA, Helminth
  • Glp-1 protein, C elegans
  • Lin-12 protein, C elegans
  • Membrane Glycoproteins
  • Membrane Proteins
  • Receptors, Notch
  • lag-2 protein, C elegans