遺傳分析C01F4.2/Arhgap6 基因於線蟲細胞吞噬作用中所扮演之角色

Abstract

Clearance of apoptotic cells is an ultimate step of programmed cell death. In C. elegans, two partially redundant signaling pathways, ced-1, ced-6, ced-7 in one, and ced-2, ced-5, ced-12 in the other, converge at CED-10, a Rho-family small GTPase, leading to actin cytoskeleton rearrangement during the engulfment of apoptotic cells. Studies in mammalian cell lines also linked the function of two additional Rho-family GTPases (RhoA and Cdc42) to phagocytosis. Recent studies suggested that the activation and inactivation of specific Rho-family proteins is important during the engulfment of apoptotic cells. These regulations should be tightly controlled spatially and temporally. In order to identify novel negative regulator for Rho-family GTPases during engulfment process, we examined 16 potential gap (GTPase-activating protein) genes that encode protein with RhoGAP domain in C. elegans and identified C01F4.2. The C01F4.2(ok1316) mutant and C01F4.2(RNAi) have increased embryonic cell corpse number compared with that of wild-type. The C01F4.2a protein is similar to human ARHGAP6 protein, which has a GTPase-activating activity specific for RhoA. The cell corpse duration analysis showed that the elevated cell corpses number in C01F4.2(ok1316) embryos was due to the defect in the clearance of apoptotic cells. Our double mutant analysis showed that the C01F4.2(ok1316) mutation did not enhance the cell-corpse number of mutants defective in either of the two previously identified engulfment pathways. Therefore C01F4.2 appear to be required functions in both pathways to regulate cell corpses engulfment. Keywords: Programmed cell death, Engulfment, Rho-family GTPases, GAP