Caspase redundancy and release of mitochondrial apoptotic factors characterize interdigital apoptosis.
Here we show a detailed analysis of cellular and molecular events during in vivo apoptotic cell death in the INZs (interdigital necrotic zones) of the embryonic limb. As the apoptotic mechanisms proceed, the transcriptionally active chromatin and nuclear traffic of RNAs are disrupted, cytoskeletal components are disorganized and the adhesive properties of cells are compromised as Paxillin, a clue member of the focal adhesion complex, decreases in early apoptotic cells. Activation of effector caspases 3 and 7 follow nuclear degradation. In addition, active caspase2 is localized in the nuclei and cytoplasm of early apoptotic cells suggesting a major role in physiological conditions supported by its down-regulation in tissue survival experiments. However in caspase 2 siRNA assays we observed translocation of caspase 3 to the nuclei suggesting functional redundancy. We also observed release of cytochrome c and AIF from the mitochondria, and interestingly AIF becomes intranuclear in a caspase independent manner.
Departamento de Anatomía y Biología Celular, Facultad de Medicina, Universidad de Cantabria, Santander 39011, Spain.
V
V
Zuzarte-Luis
M T
MT
Berciano
M
M
Lafarga
J M
JM
Hurlé
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D053143:Caspase 2; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D002467:Cell Nucleus / Q000201:enzymology / Q000378:metabolism; D002642:Chick Embryo; D045304:Cytochromes c / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D005121:Extremities / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism; D034741:RNA, Small Interfering / Q000032:analysis / Q000378:metabolism
D051033:Apoptosis Inducing Factor; D051419:Paxillin; D034741:RNA, Small Interfering; D045304:Cytochromes c; D053143:Caspase 2; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases