Genetic Analysis of C. elegans dapk-1 in the Programmed Cell Death Process
Date Issued
2006
Date
2006
Author(s)
Wang, Wei-Chun
DOI
en-US
Abstract
Programmed cell death (apoptosis) is a biological process essential for the development and homeostatic maintenance of multicellular organisms. The main genetic pathway of apoptosis governed by the genes egl-1, ced-9, ced-4, and ced-3 has been characterized in the nematode Caenorhabditis elegans and shown to be highly conserved through evolution. DAPK-1, an ortholog of human DAPK, was previously found to be a positive mediator of somatic programmed cell death in our lab. Here we analyzed dapk-1 mutants (gk219, ju4, ju469, and ju557) in detail. These mutants all exhibited reduced numbers of cell corpses generated by cell death with an allelic order: ju557 (strongest), ju469, gk219, and ju4 (weakest). ju557 was a dominant allele, while ju469 was recessive. Furthermore, the embryonic cell death of these mutants was sensitive to temperature alternation. In addition, dapk-1 mutants (gk219 and ju469) also had reduced numbers of germline cell corpses. To position dapk-1 in the genetic pathway, we expressed egl-1 ectopically in the touch neurons in different dapk-1 (gk219 and ju469) mutant backgrounds. We found that gk219 suppressed but ju469 augmented the cell-killing activity caused by egl-1overexpression. A similar result was obtained when ced-4 was overexpressed in the touch neurons in these mutants. Co-expression of dapk-1 in these cells recovered egl-1 induced cell death in gk219, suggesting that DAPK-1 functioned autonomously to promote cell death. Antibodies against DAPK-1 were generated to examine its expression pattern. DAPK-1 was widely expressed during embryogenesis. The protein exhibited a filamentous pattern in the cytoplasm and was enriched near the membrane periphery. Conclusively, DAPK-1 participates in both embryonic and germline cell death and localizes in the cytoplasm in embryonic cells. It is also indicated that this protein may play different roles depending on the cellular subset.
Subjects
線蟲
細胞死亡
C. elegans
programmed cell death
dapk-1
Type
other
File(s)![Thumbnail Image]()
Loading...
Name
ntu-95-R93b43004-1.pdf
Size
23.31 KB
Format
Adobe PDF
Checksum
(MD5):f677de6cde1edc2661ce0a23db4628d2