Getting rid of damaged goods: Loss of RhoGAP SRGP-1 promotes the clearance of dead and injured cells in C. elegans

摘要

Multicellular animals rapidly clear dying cells from the organism. 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 C. elegans and mammalian cells. Loss of srgp-1 function results in improved engulfment of apoptotic cells whereas srgp-1 over-expression inhibits apoptotic cell corpse removal. We show that SRGP-1 functions in engulfing cells and acts 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. By 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.