Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
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Τετάρτη 16 Μαΐου 2018

C. elegans Blastomeres Clear the Corpse of the Second Polar Body by LC3-Associated Phagocytosis

Publication date: 15 May 2018
Source:Cell Reports, Volume 23, Issue 7
Author(s): Gholamreza Fazeli, Maurice Stetter, Jaime N. Lisack, Ann M. Wehman
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.

Graphical abstract

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Teaser

Fazeli et al. define the rapid dynamics of cell corpse clearance in pluripotent cells, showing how dying polar bodies signal to two-cell embryos for phagocytosis. They reveal key steps in the removal of cell corpses, including LC3-mediated corpse membrane breakdown and mTOR-mediated budding of phagolysosomal vesicles to accelerate degradation.


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