title: C. elegans Rab GTPase activating protein TBC-2 promotes cell corpse degradation by regulating the small GTPase RAB-5.
abstract: During apoptosis, dying cells are quickly internalized by neighboring cells or phagocytes, and are enclosed in phagosomes that undergo a maturation process to generate the phagoslysosome, in which cell corpses are eventually degraded. It is not well understood how apoptotic cell degradation is regulated. Here we report the identification and characterization of the C. elegans tbc-2 gene, which is required for the efficient degradation of cell corpses. tbc-2 encodes a Rab GTPase activating protein (GAP) and its loss of function affects several events of phagosome maturation, including RAB-5 release, phosphatidylinositol 3-phosphate dynamics, phagosomal acidification, RAB-7 recruitment and lysosome incorporation, which leads to many persistent cell corpses at various developmental stages. Intriguingly, the persistent cell corpse phenotype of tbc-2 mutants can be suppressed by reducing gene expression of rab-5, and overexpression of a GTP-locked RAB-5 caused similar defects in phagosome maturation and cell corpse degradation. We propose that TBC-2 functions as a GAP to cycle RAB-5 from an active GTP-bound to an inactive GDP-bound state, which is required for maintaining RAB-5 dynamics on phagosomes and serves as a switch for the progression of phagosome maturation.
authors: College of Life Science, Peking University, Beijing 100871, China.
authors: Weida
authors: W
authors: Li
authors: Wei
authors: W
authors: Zou
authors: Dongfeng
authors: D
authors: Zhao
authors: Jiacong
authors: J
authors: Yan
authors: Zuoyan
authors: Z
authors: Zhu
authors: Jing
authors: J
authors: Lu
authors: Xiaochen
authors: X
authors: Wang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D017238:Genes, Helminth; D008247:Lysosomes / Q000378:metabolism; D009154:Mutation; D010588:Phagosomes / Q000378:metabolism; D010641:Phenotype; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D034622:RNA Interference; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D029742:Caenorhabditis elegans Proteins; D020690:GTPase-Activating Proteins; D018129:Phosphatidylinositol Phosphates; C055525:phosphatidylinositol 3-phosphate; D000090802:rab7 GTP-Binding Proteins; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins