西亚试剂：Sequential action of Caenorhabditis elegans Rab GTPases reg

Sequential action of Caenorhabditis elegans Rab GTPases regulates phagolysosome formation during apoptotic cell degradation
Pengfei Guoa,b,1, Tianjing Hub,1, Juan Zhangb, Shanya Jiangb, and Xiaochen Wangb,2

aSchool of Life Sciences, Peking University, Beijing 100871, China; and
bNational Institute of Biological Sciences, Beijing 102206, China

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.

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