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Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18016-21. doi: 10.1073/pnas.1008946107. Epub 2010 Oct 4.

Sequential action of Caenorhabditis elegans Rab GTPases regulates phagolysosome formation during apoptotic cell degradation.

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  • 1School of Life Sciences, Peking University, Beijing 100871, China.

Abstract

Phagocytosis of apoptotic cells requires recognition of cell corpses followed by internalization and enclosure within plasma membrane-derived phagosomes. Phagosomes undergo maturation to generate phagolysosomes in which cell corpses are degraded; however, regulation of the maturation process is poorly understood. Here, we identified Rab GTPase 14, which regulates apoptotic cell degradation in Caenorhabditis elegans. rab-14 mutants accumulate many persistent cell corpses owing to defective cell corpse clearance. Loss of rab-14 function affects several steps of phagosome maturation including phagosomal acidification and phagolysosome formation. RAB-14 and UNC-108/RAB2 are recruited to phagosomes at a similar stage and function redundantly to regulate phagosome maturation. Three Rabs, RAB-14, UNC-108/RAB2, and RAB-7, act in sequential steps to control phagolysosome formation. RAB-14 and UNC-108 recruit lysosomes, whereas RAB-7 mediates fusion of lysosomes to phagosomes. Our data reveal the sequential action of Rab GTPases in regulating tethering, docking, and fusion of lysosomes to apoptotic cell-containing phagosomes.

PMID:
20921409
[PubMed - indexed for MEDLINE]
PMCID:
PMC2964220
Free PMC Article
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