Galphao/i and Galphas signaling function in parallel with the MSP/Eph receptor to control meiotic diapause in C. elegans.
BACKGROUND
A conserved biological feature of sexual reproduction in animals is that oocytes arrest in meiotic prophase and resume meiosis in response to extraovarian signals. In C. elegans, sperm trigger meiotic resumption by means of the major sperm protein (MSP) signal. MSP promotes meiotic resumption by functioning as an ephrin-signaling antagonist and by counteracting inhibitory inputs from the somatic gonadal sheath cells.


RESULTS
By using a genome-wide RNAi screen in a female-sterile genetic background, we identified 17 conserved genes that maintain meiotic arrest in the absence of the MSP signal. In vitro binding experiments show that MSP promotes oocyte mitogen-activated protein kinase activation and meiotic maturation in part through direct interaction with the VAB-1 Eph receptor. Four conserved proteins, including a disabled protein (DAB-1), a vav family GEF (VAV-1), a protein kinase C (PKC-1), and a STAM homolog (PQN-19), function with the VAB-1 Eph/MSP receptor in oocytes. We show that antagonistic Galphao/i and Galphas signaling pathways function in the soma to regulate meiotic maturation in parallel to the VAB-1 pathway. Galphas activity is necessary and sufficient to promote meiotic maturation, which it does in part by antagonizing inhibitory sheath/oocyte gap-junctional communication.


CONCLUSIONS
Our findings show that oocyte Eph receptor and somatic cell G protein signaling pathways control meiotic diapause in C. elegans, highlighting contrasts and parallels between MSP signaling in C. elegans and luteinizing hormone signaling in mammals.
Govindan
J Amaranath
JA
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 465 21st Avenue South, Nashville, Tennessee 37232, USA.
Cheng
Hua
H
Harris
Jana E
JE
Greenstein
David
D
D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D015801:Helminth Proteins / Q000378:metabolism*; D008322:Mammals / Q000378:metabolism; D008540:Meiosis / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism; D034622:RNA Interference; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D036081:Receptors, Eph Family / Q000378:metabolism*; D015398:Signal Transduction
D033942:Adaptor Proteins, Vesicular Transport; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C510381:DAB-1 protein, C elegans; D015801:Helminth Proteins; C050602:major sperm protein, nematode; D020794:Receptor Protein-Tyrosine Kinases; D036081:Receptors, Eph Family; C111040:vab-1 protein, C elegans; D020928:Mitogen-Activated Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs