The adaptor-like protein ROG-1 is required for activation of the Ras-MAP kinase pathway and meiotic cell cycle progression in Caenorhabditis elegans

Genes Cells. 2007 Mar;12(3):407-20. doi: 10.1111/j.1365-2443.2007.01061.x.

Abstract

The Ras-MAP kinase pathway regulates varieties of fundamental cellular events. In Caenorhabditis elegans, this pathway is required for oocyte development; however, the nature of its up-stream regulators has remained elusive. Here, we identified a C. elegans gene, rog-1, which encodes the only protein having the IRS-type phosphotyrosine-binding (PTB) domain in the worms. ROG-1 has no obvious domain structure aside from the PTB domain, suggesting that it could serve as an adaptor down-stream of protein-tyrosine kinases (PTKs). RNA interference (RNAi)-mediated down-regulation of rog-1 mRNA significantly decreased brood size. rog-1(tm1031) truncation mutants showed a severe disruption in progression of developing oocytes from pachytene to diakinesis, as was seen in worms carrying a loss-of-function mutation in the let-60 Ras or mpk-1 MAP kinase gene. Furthermore, let-60 Ras-regulated activation of MPK-1 in the gonad is undetectable in rog-1(tm1031) mutants. Conversely, a gain-of-function mutation in the let-60 Ras gene rescues the brood size reduction and germ cell abnormality in rog-1(tm1031) worms. Consistently, rog-1 is preferentially expressed in the germ cells and its expression in the gonad is essential for oocyte development. Thus, ROG-1 is a key positive regulator of the Ras-MAP kinase pathway that permits germ cells to exit from pachytene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA, Helminth / genetics
  • Female
  • Genes, Helminth
  • MAP Kinase Signaling System*
  • Male
  • Meiosis / genetics
  • Meiosis / physiology*
  • Mitogen-Activated Protein Kinase 1
  • Molecular Sequence Data
  • Mutation
  • Oogenesis
  • Phylogeny
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • DNA, Helminth
  • RNA, Messenger
  • let-60 protein, C elegans
  • Protein Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase 1
  • mpk-1 protein, C elegans
  • ras Proteins