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Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover

The cytoskeletal protein actin plays a critical role in the pathogenicity of Toxoplasma gondii, mediating invasion and egress, cargo transport, and organelle inheritance. Advances in live cell imaging have revealed extensive filamentous actin networks in the Apicomplexan parasite, but there is confl...

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Autores principales: Hvorecny, Kelli L., Sladewski, Thomas E., De La Cruz, Enrique M., Kollman, Justin M., Heaslip, Aoife T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491163/
https://www.ncbi.nlm.nih.gov/pubmed/37693530
http://dx.doi.org/10.1101/2023.08.29.555340
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author Hvorecny, Kelli L.
Sladewski, Thomas E.
De La Cruz, Enrique M.
Kollman, Justin M.
Heaslip, Aoife T.
author_facet Hvorecny, Kelli L.
Sladewski, Thomas E.
De La Cruz, Enrique M.
Kollman, Justin M.
Heaslip, Aoife T.
author_sort Hvorecny, Kelli L.
collection PubMed
description The cytoskeletal protein actin plays a critical role in the pathogenicity of Toxoplasma gondii, mediating invasion and egress, cargo transport, and organelle inheritance. Advances in live cell imaging have revealed extensive filamentous actin networks in the Apicomplexan parasite, but there is conflicting data regarding the biochemical and biophysical properties of Toxoplasma actin. Here, we imaged the in vitro assembly of individual Toxoplasma actin filaments in real time, showing that native, unstabilized filaments grow tens of microns in length. Unlike skeletal muscle actin, Toxoplasma filaments intrinsically undergo rapid treadmilling due to a high critical concentration, fast monomer dissociation, and rapid nucleotide exchange. Cryo-EM structures of stabilized and unstabilized filaments show an architecture like skeletal actin, with differences in assembly contacts in the D-loop that explain the dynamic nature of the filament, likely a conserved feature of Apicomplexan actin. This work demonstrates that evolutionary changes at assembly interfaces can tune dynamic properties of actin filaments without disrupting their conserved structure.
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spelling pubmed-104911632023-09-09 Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover Hvorecny, Kelli L. Sladewski, Thomas E. De La Cruz, Enrique M. Kollman, Justin M. Heaslip, Aoife T. bioRxiv Article The cytoskeletal protein actin plays a critical role in the pathogenicity of Toxoplasma gondii, mediating invasion and egress, cargo transport, and organelle inheritance. Advances in live cell imaging have revealed extensive filamentous actin networks in the Apicomplexan parasite, but there is conflicting data regarding the biochemical and biophysical properties of Toxoplasma actin. Here, we imaged the in vitro assembly of individual Toxoplasma actin filaments in real time, showing that native, unstabilized filaments grow tens of microns in length. Unlike skeletal muscle actin, Toxoplasma filaments intrinsically undergo rapid treadmilling due to a high critical concentration, fast monomer dissociation, and rapid nucleotide exchange. Cryo-EM structures of stabilized and unstabilized filaments show an architecture like skeletal actin, with differences in assembly contacts in the D-loop that explain the dynamic nature of the filament, likely a conserved feature of Apicomplexan actin. This work demonstrates that evolutionary changes at assembly interfaces can tune dynamic properties of actin filaments without disrupting their conserved structure. Cold Spring Harbor Laboratory 2023-08-30 /pmc/articles/PMC10491163/ /pubmed/37693530 http://dx.doi.org/10.1101/2023.08.29.555340 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Hvorecny, Kelli L.
Sladewski, Thomas E.
De La Cruz, Enrique M.
Kollman, Justin M.
Heaslip, Aoife T.
Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover
title Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover
title_full Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover
title_fullStr Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover
title_full_unstemmed Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover
title_short Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover
title_sort toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491163/
https://www.ncbi.nlm.nih.gov/pubmed/37693530
http://dx.doi.org/10.1101/2023.08.29.555340
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