8.A.68.1.14
The Gm364 protein of 671 aas and 10 TMSs in a 1 + 1 + 2 + 2 + 2 + 2 TMS arrangement. Gm364 coordinates MIB2/DLL3/Notch2 to regulate female fertility through AKT activation (Chen et al. 2021). Global knockout of Gm364 decreased the numbers of primordial follicles and growing follicles, impaired oocyte quality as indicated by increased ROS and gamma-H2AX, decreased mitochondrial membrane potential, decreased oocyte maturation, and increased aneuploidy. Mechanistically, Gm364 directly binds and anchors MIB2, a ubiquitin ligase, on the membrane. Subsequently, membrane MIB2 ubiquitinates and activates DLL3. Next, the activated DLL3 binds and activates Notch2, which is subsequently cleaved within the cytoplasm to produce NICD2, the intracellular active domain of Notch2. Finally, NICD2 can directly activate AKT within the cytoplasm to regulate oocyte meiosis and quality (Chen et al. 2021).