C. elegansRab GTPase activating protein TBC-2 promotes cell corpse degradation by regulating the small GTPase RAB-5
Citations Over TimeTop 17% of 2009 papers
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.
Related Papers
- → An ARF6/Rab35 GTPase Cascade for Endocytic Recycling and Successful Cytokinesis(2012)165 cited
- → Phagocytic Receptor CED-1 Initiates a Signaling Pathway for Degrading Engulfed Apoptotic Cells(2008)124 cited
- → Sequential action of Caenorhabditis elegans Rab GTPases regulates phagolysosome formation during apoptotic cell degradation(2010)89 cited
- → Rab GTPases act in sequential steps to regulate phagolysosome formation(2010)14 cited
- → Faculty Opinions recommendation of Phagocytic receptor CED-1 initiates a signaling pathway for degrading engulfed apoptotic cells.(2008)