The adaptor-like protein ROG-1 is required for activation of the Ras-MAP kinase pathway and meiotic cell cycle progression in Caenorhabditis elegans.
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.
Matsubara
Yosuke
Y
Department of Cell Regulation, Medical Research Institute, Tokyo, Japan.
Kawasaki
Ichiro
I
Urushiyama
Seiichi
S
Yasuda
Tomoharu
T
Shirakata
Masaki
M
Iino
Yuichi
Y
Shibuya
Hiroshi
H
Yamanashi
Yuji
Y
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018509:DNA, Helminth / Q000235:genetics; D005260:Female; D017238:Genes, Helminth; D020935:MAP Kinase Signaling System; D008297:Male; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1; D008969:Molecular Sequence Data; D009154:Mutation; D009866:Oogenesis; D010802:Phylogeny; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D012333:RNA, Messenger; C066646:let-60 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; C085697:mpk-1 protein, C elegans; D018631:ras Proteins