Genetic analysis in Caenorhabditis elegans has identified several genes needed for the engulfment of apoptotic cells. Additional components have been identified through the study of phagocytosis in mammalian macrophages. For example, CD36 is one of several transmembrane receptors needed for the engulfment of apoptotic cells by macrophages. In addition, CD36 expressed on endothelial cells mediates endothelial cell apoptosis and inhibits cell migration in response to thrombospondin-1 in the extracellular matrix. We find that CD36-like genes in C. elegans are also needed for engulfment of programmed cell deaths and for the migration of the anterior arm of the gonad. C. elegans has six CD36-like proteins: C03F11.3, Y49E10.20, Y76A2B.6, F11C1.3, F07A5.3, and R07B1.3. Bacteria-mediated RNAi, which we found to be superior to injection of dsRNA, revealed a germline cell corpse engulfment defect for Y49E10.20 and Y76A2B.6 but not C03F11.3, R07B1.3, F07A5.3, F11C1.3,
unc-22 , or the empty vector control. RNA interference of Y76A2B.6 also delayed embryonic corpse clearance in the three-fold embryo. In addition, RNAi of Y49E10.20 and Y76A2B.6 caused inappropriate migration of the anterior arm of the gonad. GFP gene and promoter fusions with Y76A2B.6 are expressed in hypodermal cells, which are known to engulf apoptotic cells. A Y49E10.20 promoter fusion to GFP is expressed in many cells in the three-fold embryo, in the head and tail of L1 larvae, and in the hypodermis throughout development, consistent with functions in apoptosis and engulfment. C03F11.3 promoter and gene fusions are expressed in the intestine. Since the thrombospondin
type-1 repeat of UNC-5 is required to rescue
unc-5(
e53) mutants and
unc-5 animals have defective gonad arm migration, we examined whether RNAi of CD36-like proteins could enhance this phenotype. We also looked for potential genetic interactions between CD36-like proteins and cell death engulfment mutants in both genetically determined engulfment pathways. Bacterial RNAi of the six candidates did not enhance either the
unc-5 gonad arm migration defect or the somatic engulfment phenotype of
ced-1 or
ced-5 . Because integrins are known to cooperate with CD36 in the binding and internalization of apoptotic cells by macrophages, we also examined
ina-1 , an a -integrin mutant, for an engulfment phenotype.
ina-1(
gm199) does produce a germline cell death engulfment phenotype which can be enhanced by bacterial-mediated RNA interference of either Y49E10.20 or F11C1.3.