TY - JOUR
T1 - Loss of the RhoGAP SRGP-1 promotes the clearance of dead and injured cells in Caenorhabditis elegans
AU - Neukomm, Lukas J.
AU - Frei, Andreas P.
AU - Cabello, Juan
AU - Kinchen, Jason M.
AU - Zaidel-Bar, Ronen
AU - Ma, Zhong
AU - Haney, Lisa B.
AU - Hardin, Jeff
AU - Ravichandran, Kodi S.
AU - Moreno, Sergio
AU - Hengartner, Michael O.
N1 - Funding Information:
We thank the Hengartner lab members for comments and discussions, M. Weiss for statistical advice and M. Jovanovic for assistance with in vivo pulldown experiments. Some strains were supplied by the Caenorhabditis Genetic Center (CGC), the C. elegans knock-out consortium (Oklahoma, USA) and the National Bioresource Project (Japan). This work was supported by grants from the American Heart Association and American Cancer Society (to J.M.K.), the NIGMS/NIH (to K.S.R., a William Benter Senior Fellow of the American Asthma Foundation), the Junta de Castilla y León (grant CSI03A08), the Spanish Ministry of Science and Innovation (grant BFU2010-21794) and the Riojasalud Foundation (to J.C.), the Junta de Castilla y León (Grupo de Excelencia GR265) and the Spanish Ministry of Science and Innovation (grants BFU200801808 and Consolider CSD200700015 to S.M.), the NIH postdoctoral training grant GM078747 and the fellowship from the Machiah Foundation (to R.Z.-B.), the Swiss National Science Foundation, The Ernst Hadorn Foundation and the European Union (FP5 project APOCLEAR to M.O.H.).
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78650512821&partnerID=8YFLogxK
U2 - 10.1038/ncb2138
DO - 10.1038/ncb2138
M3 - Article
C2 - 21170032
AN - SCOPUS:78650512821
SN - 1465-7392
VL - 13
SP - 79
EP - 86
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 1
ER -