Disassembly activity of actin depolymerization factor (ADF) is associated with distinct cellular processes in apicomplexan parasites
Autor: | Rebecca Stewart, David R. Kovar, Christopher J. Tonkin, Yan-Hong Tan, Wilson Wong, Mark E Wilkinson, Maya A. Olshina, Silvia Haase, Jake Baum, Fabio R. Fisher, Dennis Zimmermann |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Gliding motility
Plasmodium falciparum Motility macromolecular substances Biology Gene Knockout Techniques Cell Movement parasitic diseases Animals Cytoskeleton Molecular Biology Actin Genetic Association Studies Lysine Cell Biology Articles Cofilin Actin cytoskeleton Actins 3. Good health Cell biology Actin Cytoskeleton Destrin Actin depolymerizing factor Toxoplasma |
Zdroj: | Molecular Biology of the Cell |
Popis: | Complementation of a conditional KO of actin-depolymerizing factor (ADF) in Toxoplasma gondii demonstrates that ADF-dependent actin filament disassembly is essential for parasite development but not for cell motility. Furthermore, trans-genera complementation highlights genus-specific coevolution between ADF proteins and their native actins. Proteins of the actin-depolymerizing factor (ADF)/cofilin family have been shown to be crucial for the motility and survival of apicomplexan parasites. However, the mechanisms by which ADF proteins fulfill their function remain poorly understood. In this study, we investigate the comparative activities of ADF proteins from Toxoplasma gondii and Plasmodium falciparum, the human malaria parasite, using a conditional T. gondii ADF-knockout line complemented with ADF variants from either species. We show that P. falciparum ADF1 can fully restore native TgADF activity, demonstrating functional conservation between parasites. Strikingly, mutation of a key basic residue (Lys-72), previously implicated in disassembly in PfADF1, had no detectable phenotypic effect on parasite growth, motility, or development. In contrast, organelle segregation was severely impaired when complementing with a TgADF mutant lacking the corresponding residue (Lys-68). Biochemical analyses of each ADF protein confirmed the reduced ability of lysine mutants to mediate actin depolymerization via filament disassembly although not severing, in contrast to previous reports. These data suggest that actin filament disassembly is essential for apicomplexan parasite development but not for motility, as well as pointing to genus-specific coevolution between ADF proteins and their native actin. |
Databáze: | OpenAIRE |
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