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Fig. 5. Working models of the MSP signaling mechanism. MSP binds to multiple receptors on the oocyte plasma membrane (PM), including the VAB-1 Eph receptor. (A) When extracellular MSP is scarce or absent, ephrin/VAB-1- and CEH-18-dependent pathways negatively regulate MPK-1 MAPK activation and oocyte maturation. The ITR-1 IP3 receptor acts downstream of VAB-1, while the NMR-1 NMDA-receptor subunit prevents activation of UNC-43 CaMKII. (B) MSP binding to VAB-1 triggers a switch (SW) from negative to positive regulation. As a result, NMR-1 stimulates UNC-43 T284 phosphorylation and signaling at the oocyte cortex. MSP also binds to unidentified MSP receptors (MSPRs) that act redundantly to promote oocyte maturation. MSPRs could function in oocytes (shown), sheath cells or both. Broken lines indicate downregulated pathways. See text for details. Models are based on results from this study and previous studies. SW, switch; GJ, gap junction; TF, transcription factor; IP3R, inositol triphosphate receptor.





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