MSP hormonal control of the oocyte MAP kinase cascade and reactive oxygen species signaling

Abstract

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.

C. elegans STK39/SPAK ortholog-mediated inhibition of ClC anion channel activity is regulated by WNK-independent ERK kinase signaling

“…Major sperm protein is thought to activate MPK-1, which in turn induces meiotic maturation (37,55). However, as maturation proceeds, activated MPK-1 levels fall rapidly and dramatically (31).…”

The regulation of spermatogenesis and sperm function in nematodes

“…VAB-1 functionally interacts with multiple intracellular Ca ++ regulators [127], but how these interactions couple to the MAPK cascade is not well understood. Components of a conventional receptor tyrosine kinase (RTK) pathway, including the Shp protein tyrosine phosphatase PTP-2, are essential for MAPK activation [128]. However, this unidentified RTK is not likely to be VAB-1.…”

The eggshell in the C. elegans oocyte‐to‐embryo transition

“…Within the CL, a band of higher electron density just below the VL suggests the presence of distinct CL sublayers. The extraembryonic matrix (EEM) separates the eggshell from the embryo plasma membrane, and has two distinct bands visible by EM: an outer clear zone and an inner fibrous embryonic layer (EmL) (Benenati et al, 2009). is released from sperm in the spermatheca and diffuses into the proximal gonad, where it signals to relieve MAPK inhibition and allow meiotic progression Miller et al, 2003;Yang et al, 2010). Progression also requires relief of inhibition of maturation promoting factor (MPF), comprised of CDK-1 and cyclin B3.…”