RRC ID 6392
Author Li W, Zou W, Zhao D, Yan J, Zhu Z, Lu J, Wang X.
Title C. elegans Rab GTPase activating protein TBC-2 promotes cell corpse degradation by regulating the small GTPase RAB-5.
Journal Development
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.
Volume 136(14)
Pages 2445-55
Published 2009-7-1
DOI 10.1242/dev.035949
PII 136/14/2445
PMID 19542357
MeSH Animals Animals, Genetically Modified Apoptosis / genetics Apoptosis / physiology* Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* GTPase-Activating Proteins / genetics GTPase-Activating Proteins / metabolism* Genes, Helminth Lysosomes / metabolism Mutation Phagosomes / metabolism Phenotype Phosphatidylinositol Phosphates / metabolism RNA Interference rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism rab5 GTP-Binding Proteins / genetics rab5 GTP-Binding Proteins / metabolism* rab7 GTP-Binding Proteins
IF 5.611
Times Cited 37
C.elegans tm2241