The Role of Dynamin in the Clearance of Apoptotic Cells

Abstract

In animals, cells undergoing apoptosis are rapidly engulfed and degraded by phagocytes. The removal of apoptotic cells provides a safe means for eliminating unwanted and dangerous cells from the body. Furthermore, it prevents tissue injury, and inflammatory and auto‐immune responses induced by the lingering dead cells. In a genetic screen for mutations that affect the removal of apoptotic cells in the nematode C. elegans. We isolated fourteen loss‐of‐function alleles of dyn‐1, which encodes the C. elegans ortholog of large GTPase dynamin. Our cell biological characterizations indicate that DYN‐1 is essential for both the engulfment and degradation of apoptotic cells. DYN‐1 promotes the incorporation of endosomes to the extending pseudopods during engulfment, and the recruitment and incorporation of both endosomes and lysosomes to phagosomes containing apoptotic cells. Phosphatidylinositol 3‐phosphate (PI(3)P) and the small GTPase RAB‐7 mediate the specific function of DYN‐1 in phagosome maturation. Our in vitro and in vivo analyses demonstrate that the GTP hydrolysis and self‐assembly activities of DYN‐1 control distinct aspects of DYN‐1's function in phagosome maturation. Furthermore, the phagocytic receptor CED‐1 recruits DYN‐1 to the site of engulfment. These findings indicate that DYN‐1 is a key component of a pathway that regulates vesicle transport during the removal of apoptotic cells.