Regulated trafficking of the MSP/Eph receptor during oocyte meiotic maturation in C. elegans.
BACKGROUND
In C. elegans, a sperm-sensing mechanism regulates oocyte meiotic maturation and ovulation, tightly coordinating sperm availability and embryo production; sperm release the major sperm protein (MSP) signal to trigger meiotic resumption. Meiotic arrest depends on the parallel function of the oocyte VAB-1 MSP/Eph receptor and somatic G protein signaling. MSP promotes meiotic maturation by antagonizing Eph receptor signaling and counteracting inhibitory inputs from the gonadal sheath cells.


RESULTS
Here, we present evidence suggesting that in the absence of the MSP ligand, the VAB-1 Eph receptor inhibits meiotic maturation while either in or in transit to the endocytic-recycling compartment. VAB-1::GFP localization to the RAB-11-positive endocytic-recycling compartment is independent of ephrins but is antagonized by MSP signaling. Two negative regulators of oocyte meiotic maturation, DAB-1/Disabled and RAN-1, interact with the VAB-1 receptor and are required for its accumulation in the endocytic-recycling compartment in the absence of MSP or sperm (hereafter referred to as MSP/sperm). Inactivation of the endosomal recycling regulators rme-1 or rab-11.1 causes a vab-1-dependent reduction in the meiotic-maturation rate in the presence of MSP/sperm. Further, we show that Galpha(s) signaling in the gonadal sheath cells, which is required for meiotic maturation in the presence of MSP/sperm, affects VAB-1::GFP trafficking in oocytes.


CONCLUSIONS
Regulated endocytic trafficking of the VAB-1 MSP/Eph receptor contributes to the control of oocyte meiotic maturation in C. elegans. Eph receptor trafficking in other systems may be influenced by the conserved proteins DAB-1/Disabled and RAN-1 and by crosstalk with G protein signaling in neighboring cells.
Cheng
Hua
H
Department of Genetics, Cell Biology and Development, University of Minnesota, 6-160 Jackson Hall, 321 Church Street SE, Minneapolis, Minnesota 55455; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Govindan
J Amaranath
JA
Department of Genetics, Cell Biology and Development, University of Minnesota, 6-160 Jackson Hall, 321 Church Street SE, Minneapolis, Minnesota 55455; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Greenstein
David
D
Department of Genetics, Cell Biology and Development, University of Minnesota, 6-160 Jackson Hall, 321 Church Street SE, Minneapolis, Minnesota 55455. Electronic address: green959@umn.edu.
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004705:Endocytosis; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D015801:Helminth Proteins / Q000378:metabolism*; D008297:Male; D008540:Meiosis / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D010060:Ovulation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013094:Spermatozoa / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D033942:Adaptor Proteins, Vesicular Transport; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D019205:GTP-Binding Protein alpha Subunits, Gs; D049452:Green Fluorescent Proteins; D015801:Helminth Proteins; D009687:Nuclear Proteins; D020794:Receptor Protein-Tyrosine Kinases; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C510381:DAB-1 protein, C elegans; C050602:major sperm protein, nematode; C091775:ran-binding protein 1; C111040:vab-1 protein, C elegans