After apoptosis occurs, apoptotic cells must be cleared quickly, and the clearance defects of apoptotic cells can lead to inflammation and autoimmune diseases. Apoptotic cells are first engulfed by phagocytes and form phagosomes. The phagosomes undergo a gradual maturation process, and finally fuse with lysosomes and are degraded. Autophagy is another important biological process in cells, which can degrade damaged organelles and misfolded proteins in cells to maintain the homeostasis of cells and the body.
The study took Caenorhabditis elegans as the research object, and found that in the embryonic development stage of C. elegans, the absence of almost any autophagy protein will cause defects in the clearance of apoptotic cells, and specifically affect the receptors of certain substrate degradation Or the lack of bridge protein will not affect the clearance of apoptotic cells. Further research showed that the process of apoptotic cell recognition and endocytosis was not affected, but the maturation process of phagosomes was delayed.
The production and maintenance of Ptdlns(3)P play an important role in the formation and maturation of phagosomes. Ptdlns(3)P in nematodes is mainly produced by PIKI-1 and VPS-34 kinases. Genetic analysis showed that in the process of clearing apoptotic cells, autophagy protein played a role in parallel with PIKI-1, and played a role in the same path as VPS-34. Through sequential imaging analysis, we found that the loss of PIKI-1 will affect the initial production of Ptdlns(3)P, while the loss of autophagy protein or VPS-34 will affect the maintenance of Ptdlns(3)P. Moreover, in the double mutant of piki-1 and autophagy gene, the appearance of Ptdlns(3)P was more significantly affected. Since VPS-34 participates in both the maturation of phagosomes and autophagy, we speculate that the defects of autophagy may cause the disorder of VPS-34 function, thereby affecting its role in the maturation of phagosomes.
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