C. elegans Blastomeres Clear the Corpse of the Second Polar Body by LC3-Associated Phagocytosis
Gholamreza Fazeli1, Maurice Stetter1, Jaime N Lisack1
1Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, 97080 Würzburg, Germany.
Abstract:
To understand how undifferentiated pluripotent cells cope with cell corpses, we examined the clearance of polar bodies born during female meiosis. We found that polar bodies lose membrane integrity and expose phosphatidylserine in Caenorhabditis elegans. Polar body signaling recruits engulfment receptors to the plasma membrane of embryonic blastomeres using the PI3K VPS-34, RAB-5 GTPase and the sorting nexin SNX-6. The second polar body is then phagocytosed using receptor-mediated engulfment pathways dependent on the Rac1 ortholog CED-10 but undergoes non-apoptotic programmed cell death independent of engulfment. RAB-7 GTPase is required for lysosome recruitment to the polar body phagosome, while LC3 lipidation is required for degradation of the corpse membrane after lysosome fusion. The polar body phagolysosome vesiculates in an mTOR- and ARL-8-dependent manner, which assists its timely degradation. Thus, we established a genetic model to study clearance by LC3-associated phagocytosis and reveal insights into the mechanisms of phagosome maturation and degradation.
Insights
Undifferentiated cells clear cell corpses, like polar bodies during meiosis, through a process called LC3-associated phagocytosis. This involves specific proteins that guide engulfment and degradation.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Pluripotent stem cells must efficiently clear cellular debris to maintain their undifferentiated state.
- Understanding the mechanisms of corpse clearance is crucial for developmental processes and stem cell research.
Purpose of the Study:
- To investigate how undifferentiated pluripotent cells in Caenorhabditis elegans handle cell corpses, specifically polar bodies during female meiosis.
- To elucidate the genetic and molecular pathways involved in the phagocytosis and degradation of these corpses.
Main Methods:
- Utilized Caenorhabditis elegans as a genetic model system.
- Examined the process of polar body clearance using live imaging and genetic screens.
- Investigated the roles of specific proteins, including PI3K VPS-34, RAB-5, SNX-6, CED-10, RAB-7, LC3, mTOR, and ARL-8.
Main Results:
- Polar bodies lose membrane integrity and expose phosphatidylserine, signaling for engulfment.
- Receptor-mediated phagocytosis pathways, dependent on CED-10, are involved in clearing the second polar body.
- Lysosome recruitment (RAB-7) and LC3 lipidation are essential for phagosome maturation and corpse degradation.
- Phagolysosome vesiculation, regulated by mTOR and ARL-8, facilitates timely degradation.
Conclusions:
- Established a genetic model for studying LC3-associated phagocytosis in the context of polar body clearance.
- Revealed novel insights into the molecular mechanisms governing phagosome maturation and degradation by pluripotent cells.
- Highlighted the importance of efficient corpse clearance for cellular homeostasis during development.
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