The ced-8 Gene Controls the Timing of Programmed Cell Deaths in C. elegans

Abstract

Loss-of-function mutations in the gene ced-8 lead to the late appearance of cell corpses during embryonic development in C. elegans. ced-8 functions downstream of or in parallel to-the regulatory cell death gene ced-9 and may function as a cell death effector downstream of the caspase encoded by the programmed cell death killer gene ced-3. In ced-8 mutants, embryonic programmed cell death probably initiates normally but proceeds slowly. ced-8 encodes a transmembrane protein that appears to be localized to the plasma membrane. The CED-8 protein is similar to human XK, a putative membrane transport protein implicated in McLeod Syndrome, a form of hereditary neuroacanthocytosis.

DPL-1 DP, LIN-35 Rb and EFL-1 E2F Act With the MCD-1 Zinc-Finger Protein to Promote Programmed Cell Death inCaenorhabditis elegans

“…We observed that mutations in mcd-1 and dpl-1 enhanced cell-killing defects conferred by ced-1(e1735) or ced-8(n1891) ( Table 3C). Because ced-1(e1735) and ced-8(n1891) are both null or strong loss-of-function alleles (Stanfield and Horvitz 2000;Zhou et al 2001), our data indicate that mcd-1 and dpl-1 act independently from ced-8 and ced-1. Furthermore, we examined doubly mutant strains carrying a wild-type ced-3 locus and observed enhanced cell-death defects: ced-1(e1735); dpl-1(n3380) animals, ced-1(e1735); mcd-1(n3376) animals, dpl-1(n3380); ced-8(n1891) animals, and mcd-1(n3376); ced-8(n1891) animals had defects in cell killing greater than those seen in the single mutants (supplemental Table S2C and supplemental Figure S2F at www.genetics.org/supplemental/).…”

“…Mutations in engulfment genes (e.g., ced-1) can decrease cell killing (Reddien et al 2001). Mutations in ced-8 cause a delay in cell death, enhance weak alleles of ced-3, and cause very weak defects in cell killing on their own (Stanfield and Horvitz 2000). We observed that mutations in mcd-1 and dpl-1 enhanced cell-killing defects conferred by ced-1(e1735) or ced-8(n1891) ( Table 3C).…”

“…For example, the gene ced-8 XK affects the timing of programmed cell deaths in C. elegans and has a minor role in cell killing (Stanfield and Horvitz 2000). The gene ced-9, which inhibits programmed cell death, also can promote cell death (Hengartner and Horvitz 1994a).…”

Overlapping BXSB congenic intervals, in combination with microarray gene expression, reveal novel lupus candidate genes

“…It may function to degrade DNA during apoptosis, in a pathway parallel to the Ced9 pathway. 36 Defects in apoptosis have been demonstrated to affect the availability of autoantigens which drive autoantibody production, 37 and genes in the apoptotic pathway, such as Fas, have been implicated in the development of lupus in the MRL model. 38 The Bxs3 locus is homologous to Nba2 in (NZB Â NZW)F 1 11 and Sle1 in NZM2410, two models based on the New Zealand mouse.…”

Mechanisms of apoptotic phosphatidylserine exposure

“…Finally, the authors moved to the nematode Caenorhabditis elegans to analyze whether the role of Xpr8 as lipid scramblase is evolutionarily conserved. C. elegans harbors only one ortholog of Xk proteins, CED-8, known to participate in the phagocytic removal of apoptotic corpses [6]. To determine the role of CED-8 in PS exposure, the authors took advantage of the "floater" assay, which is based on the appearance of floating cells ("floaters") that have detached from developing C. elegans embryos defective for apoptotic cell phagocytosis [7].…”