Clathrin-mediated endocytosis is essential for the selective degradation of maternal membrane proteins and preimplantation development

Fertilization triggers significant cellular remodeling through the oocyte-to-embryo transition. In this transition, the ubiquitin-proteasome system and autophagy are essential for the degradation of maternal components; however, the significance of degradation of cell surface components remains unknown. In this study, we show that multiple maternal plasma membrane proteins, such as the glycine transporter GlyTla, are selectively internalized from the plasma membrane to endosomes in mouse embryos by the late two-cell stage and then transported to lysosomes for degradation at the later stages. During this process, large amounts of ubiquitylated proteins accumulated on endosomes. Furthermore, the degradation of GlyTla with mutations in potential ubiquitylation sites was delayed, suggesting that ubiquitylation may be involved in GlyT1 a degradation. The clathrin inhibitor blocked GlyTla internalization. Strikingly, the protein kinase C (PKC) activator triggered the heterochronic internalization of GlyTla; the PKC inhibitor markedly blocked GlyTla endocytosis. Lastly, clathrin inhibition completely blocked embryogenesis at the two-cell stage and inhibited cell division after the four-cell stage. These findings demonstrate that PKC-dependent clathrin-mediated endocytosis is essential for the selective degradation of maternal membrane proteins during oocyte-to-embryo transition and early embryogenesis.

Automated summary

During the oocyte-to-embryo transition and early embryogenesis, PKC-dependent clathrin-mediated endocytosis is essential for the selective degradation of maternal membrane proteins.