Loss of the RhoGAP SRGP-1 promotes the clearance of dead and injured cells in Caenorhabditis elegans

• Published in: Nature cell biology Vol. 13; no. 1; pp. 79 - 86
• Main Authors: Hengartner, Michael O, Neukomm, Lukas J, Frei, Andreas P, Cabello, Juan, Kinchen, Jason M, Zaidel-Bar, Ronen, Ma, Zhong, Haney, Lisa B, Hardin, Jeff, Ravichandran, Kodi S, Moreno, Sergio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2011; Nature Publishing Group
• Subjects: 631/208/199; 631/80/82/23; Amino Acid Sequence; Animals; Animals, Genetically Modified; Apoptosis; Biomedical and Life Sciences; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cancer Research; Cell Biology; Cell Line; Cells; Cellular proteins; Death & dying; Developmental Biology; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; GTPase-Activating Proteins - genetics; GTPase-Activating Proteins - metabolism; Kinases; letter; Life Sciences; Mammals; Mice; Microscopy; Microscopy, Fluorescence; Molecular Sequence Data; Mutation; Nematodes; Neurosciences; NIH 3T3 Cells; Phagocytosis; Physiological aspects; Protein Binding; Proteins; rac GTP-Binding Proteins - genetics; rac GTP-Binding Proteins - metabolism; RNA Interference; Sequence Homology, Amino Acid; Stem Cells; Survival; Switzerland; United States > US; Spain
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb2138

Multicellular animals rapidly clear dying cells from their bodies. Many of the pathways that mediate this cell removal are conserved through evolution. Here, we identify srgp-1 as a negative regulator of cell clearance in both Caenorhabditis elegans and mammalian cells. Loss of srgp-1 function results in improved engulfment of apoptotic cells, whereas srgp-1 overexpression inhibits apoptotic cell corpse removal. We show that SRGP-1 functions in engulfing cells and functions as a GTPase activating protein (GAP) for CED-10 (Rac1). Interestingly, loss of srgp-1 function promotes not only the clearance of already dead cells, but also the removal of cells that have been brought to the verge of death through sublethal apoptotic, necrotic or cytotoxic insults. In contrast, impaired engulfment allows damaged cells to escape clearance, which results in increased long-term survival. We propose that C. elegans uses the engulfment machinery as part of a primitive, but evolutionarily conserved, survey mechanism that identifies and removes unfit cells within a tissue.