A conserved biological feature of sexual reproduction in animals is that oocytes arrest in meiotic prophase and resume meiosis in response to extra-ovarian signals. In Caenorhabditis. elegans, a sperm-sensing mechanism regulates oocyte meiotic maturation and ovulation. Sperm release the major sperm protein (MSP) signal to promotes meiotic maturation by antagonizing Eph receptor signaling and counteracting inhibitory inputs from the gonadal sheath cells. I show that MSP promotes oocyte 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 VAB-1 in oocytes. We also show that antagonistic Gáo/i and Gás signaling pathways function in the soma to regulate meiotic maturation in parallel to the VAB-1 pathway. Furthermore, I show that in the absence of MSP VAB-1 inhibits meiotic maturation while either in or in transit to the endocytic recycling compartment (ERC). VAB-1::GFP localization to the RAB-11-positive ERC 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 ERC in the absence of 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. In addition, I show that Gás signaling in the gonadal sheath cells, affects VAB-1::GFP trafficking in oocytes. Taken together, 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. Moreover, my finding suggests that regulated endocytic trafficking of the VAB-1/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 cross-talk with G-protein signaling in neighboring cells.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-11282008-174034 |
| Date | 06 December 2008 |
| Creators | cheng, hua |
| Contributors | david greenstein, Chang Chung, David Miller, Ethan Lee, Jin Chen |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-11282008-174034/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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