Phagocytosis of apoptotic cell is an integral part of the cell death program and an important cellular process in tissue remodeling, suppression of inflammation, and regulation of immune responses. Following cell death activation, apoptotic cells expose PS (phosphatidylserine), which normally is confined to the inner leaflet of plasma membrane, to the cell surface. The externalized PS can thus serve as an eat me signal for the removal of apoptotic cells. How PS eat me signal is exposed, recognized, and transduced to activate phagocytosis is not clear. Previous study in the Xue lab showed that
psr-1, the C. elegans homologue of phosphatidylserine receptor (PSR), is important for cell corpse engulfment in vivo (1). PSR-1 preferentially binds to PS in vitro and functions upstream of the CED-2, CED-5, CED-12, and CED-10 engulfment pathway. PSR-1 may function to transduce the PS engulfment signal through direct interaction of its cytoplasmic tail with CED-5 and CED-12(1). However, PSR-1 is unlikely to be the only engulfment receptor in this pathway since the
psr-1 deletion mutant (
tm469) displays much weaker engulfment defect than that of the
ced-2,
ced-5,
ced-12 and
ced-10 mutants. Identification of other engulfment receptors or components that may function in parallel to
psr-1 will help us understand how apoptotic cell is recognized and cleared. In order to identify additional factors that may function redundantly with
psr-1 to promote cell corpse engulfment, we carried out a large-scale
psr-1 enhancer screen to isolate mutations that can enhance the engulfment defect of the
psr-1 (
tm469) mutant. So far we have screened 30,000 C. elegans haploid genomes and isolated 16 candidate mutants. Three of them are alleles of the
ced-8 gene, which affects the kinetics of cell death and contains many cell corpses at late embryonic stage. Three mutations,
qx4,
qx16, and
qx20 are currently being characterized.
qx4 and
qx16 affect both the viability and the cell corpse engulfment, while
qx20 is viable. We are in the process of mapping and cloning the genes affected in these mutants. Characterization of
psr-1 enhancers may identify new players involved in the recognition and engulfment of apoptotic cells. 1. Wang, X.C., Wu, Y.C., Fadok, V., Lee, M.C., Gengyo-Ando, K., Cheng, L.C., Ledwich, D., Hsu, P.K., Chen, J.Y., Chou, B.K., Henson, P., Mitani, S., and Xue, D. (2003). Cell Corpse Engulfment Mediated by C. elegans Phosphatidylserine Receptor Through CED-5 and CED-12. Science 302, 1563-1566.