RRC ID 46659
Author Neukomm LJ, Frei AP, Cabello J, Kinchen JM, Zaidel-Bar R, Ma Z, Haney LB, Hardin J, Ravichandran KS, Moreno S, Hengartner MO.
Title Loss of the RhoGAP SRGP-1 promotes the clearance of dead and injured cells in Caenorhabditis elegans.
Journal Nat Cell Biol
Abstract 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.
Volume 13(1)
Pages 79-86
Published 2011-1-1
DOI 10.1038/ncb2138
PII ncb2138
PMID 21170032
PMC PMC3808961
MeSH Amino Acid Sequence Animals Animals, Genetically Modified Apoptosis* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Line GTPase-Activating Proteins / genetics GTPase-Activating Proteins / metabolism* Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Mice Microscopy, Fluorescence Molecular Sequence Data Mutation NIH 3T3 Cells Phagocytosis Protein Binding RNA Interference Sequence Homology, Amino Acid rac GTP-Binding Proteins / genetics rac GTP-Binding Proteins / metabolism
IF 20.042
Times Cited 41
WOS Category CELL BIOLOGY
Resource
C.elegans tm3701 tm1826 tm1949