MSP hormonal control of the oocyte MAP kinase cascade and reactive oxygen species signaling.
The MSP domain is a conserved immunoglobulin-like structure that is important for C. elegans reproduction and human motor neuron survival. C. elegans MSPs are the most abundant proteins in sperm, where they function as intracellular cytoskeletal proteins and secreted hormones. Secreted MSPs bind to multiple receptors on oocyte and ovarian sheath cell surfaces to induce oocyte maturation and sheath contraction. MSP binding stimulates oocyte MPK-1 ERK MAP Kinase (MAPK) phosphorylation, but the function and mechanism are not well understood. Here we show that the Shp class protein-tyrosine phosphatase PTP-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote MSP-induced MPK-1 phosphorylation. PTP-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. We also provide evidence that MSP promotes production of reactive oxygen species (ROS), which act as second messengers to augment MPK-1 phosphorylation. The Cu/Zn superoxide dismutase SOD-1, an enzyme that catalyzes ROS breakdown in the cytoplasm, inhibits MPK-1 phosphorylation downstream of or in parallel to ptp-2. Our results support the model that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation. We propose that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling.
Yang
Youfeng
Y
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Han
Sung Min
SM
Miller
Michael A
MA
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism; D015801:Helminth Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D015801:Helminth Proteins; D017382:Reactive Oxygen Species; C050602:major sperm protein, nematode; D020928:Mitogen-Activated Protein Kinases