1. Academic Validation
  2. Clathrin-mediated endocytosis is essential for the selective degradation of maternal membrane proteins and preimplantation development

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

  • Development. 2021 Jul 15;148(14):dev199461. doi: 10.1242/dev.199461.
Akihito Morita 1 2 Yuhkoh Satouh 1 Hidetaka Kosako 3 Hisae Kobayashi 1 Akira Iwase 2 Ken Sato 1
Affiliations

Affiliations

  • 1 Laboratory of Molecular Traffic, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, 371-8512, Japan.
  • 2 Department of Obstetrics and Gynecology, Gunma University Graduate School of Medicine, Maebashi, 371-8511, Japan.
  • 3 Division of Cell Signaling, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, 770-8503, Japan.
Abstract

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 GlyT1a, 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 GlyT1a with mutations in potential ubiquitylation sites was delayed, suggesting that ubiquitylation may be involved in GlyT1a degradation. The clathrin inhibitor blocked GlyT1a internalization. Strikingly, the protein kinase C (PKC) activator triggered the heterochronic internalization of GlyT1a; the PKC Inhibitor markedly blocked GlyT1a 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.

Keywords

Degradation; Embryogenesis; Endocytosis; Fertilization; PKC; Ubiquitylation.

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