How are dying cells recognized by those that will engulf them? It has been postulated that apoptotic cells signal to the engulfers by exposing a cell surface marker. Several potential and diverse receptors present on engulfing cells have been implicated in such a process, but identities of the ligands have remained unknown. By characterizing the membrane protein profile of normal and apoptotic T cells, Arur et al. determined that expression of the phosphatidylserine (PS)-binding protein annexin 1 was upregulated in cells upon treatment with an antibody that stimulates the Fas death receptor. This cell death trigger stimulated translocation and colocalization of cytosolic annexin 1 to PS-rich regions of the plasma membrane. Treatment of cells with a caspase inhibitor blocked apoptosis and annexin 1 externalization. Down-regulation of annexin 1 expression in T cells by small interfering RNA reduced tethering of T cells to engulfing endothelial cells, but addition of soluble annexin 1 rescued tethering. Decreased expression of a receptor for PS (PSR) in endothelial cells also reduced tethering to apoptotic T cells. Finally, down-regulation of an annexin 1 homolog in Caenorhabditis elegans prevented engulfment of cell corpses. The authors propose that annexin 1-mediated signals are transmitted by PSR to induce the engulf response.
S. Arur, U. E. Uche, K. Rezaul, M. Fong, V. Scranton, A. E. Cowan, W. Mohler, D. K. Han, Annexin I is an endogenous ligand that mediates apoptotic cell engulfment. Dev. Cell 4, 587-598 (2003). [Online Journal]