The N-terminal fragment of gelsolin inhibits the interaction of DNase I with isolated actin, but not with the cofilin-actin complex.
Apoptosis is essential in embryonic development, clonal selection of cells of the immune system and in the prevention of cancer. Apoptotic cells display characteristic changes in morphology that precede the eventual fragmentation of nuclear DNA resulting in cell death. Current evidence implicates DNase I as responsible for hydrolysis of DNA during apoptosis. In vivo, it is likely that cytoplasmic actin binds and inhibits the enzymatic activity and nuclear translocation of DNase I and that disruption of the actin-DNase I complex results in activation of DNase I. In this report we demonstrate that the N-terminal fragment of gelsolin (N-gelsolin) disrupts the actin-DNase I interaction. This provides a molecular mechanism for the role of the N-gelsolin in regulating DNase I activity. We also show that cofilin stabilises the actin-DNase I complex by forming a ternary complex that prevents N-gelsolin from releasing DNase I from actin. We suggest that both cofilin and gelsolin are essential in modulating the release of DNase I from actin.
Chhabra
Deepak
D
Muscle Research Unit, Institute for Biomedical Research, School of Medical Sciences, University of Sydney, NSW 2006, Australia.
Nosworthy
Neil J
NJ
dos Remedios
Cristobal G
CG
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000737:chemistry*; D000495:Allosteric Site; D000818:Animals; D017209:Apoptosis; D001717:Birds; D016923:Cell Death; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D003850:Deoxyribonuclease I / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000378:metabolism; D005456:Fluorescent Dyes / Q000494:pharmacology; D018260:Gelsolin / Q000737:chemistry*; D006801:Humans; D006868:Hydrolysis; D008840:Microfilament Proteins / Q000737:chemistry*; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry
D051339:Actin Depolymerizing Factors; D000199:Actins; D005456:Fluorescent Dyes; D018260:Gelsolin; D008840:Microfilament Proteins; D011994:Recombinant Proteins; D004247:DNA; D003850:Deoxyribonuclease I