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Identification and Molecular Dissection of IMC32, a Conserved Toxoplasma Inner Membrane Complex Protein That Is Essential for Parasite Replication

The inner membrane complex (IMC) is a unique organelle of apicomplexan parasites that plays critical roles in parasite motility, host cell invasion, and replication. Despite the common functions of the organelle, relatively few IMC proteins are conserved across the phylum and the precise roles of ma...

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Detalles Bibliográficos
Autores principales: Torres, Juan A., Pasquarelli, Rebecca R., Back, Peter S., Moon, Andy S., Bradley, Peter J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545131/
https://www.ncbi.nlm.nih.gov/pubmed/33593973
http://dx.doi.org/10.1128/mBio.03622-20
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author Torres, Juan A.
Pasquarelli, Rebecca R.
Back, Peter S.
Moon, Andy S.
Bradley, Peter J.
author_facet Torres, Juan A.
Pasquarelli, Rebecca R.
Back, Peter S.
Moon, Andy S.
Bradley, Peter J.
author_sort Torres, Juan A.
collection PubMed
description The inner membrane complex (IMC) is a unique organelle of apicomplexan parasites that plays critical roles in parasite motility, host cell invasion, and replication. Despite the common functions of the organelle, relatively few IMC proteins are conserved across the phylum and the precise roles of many IMC components remain to be characterized. Here, we identify a novel component of the Toxoplasma gondii IMC (IMC32) that localizes to the body portion of the IMC and is recruited to developing daughter buds early during endodyogeny. IMC32 is essential for parasite survival, as its conditional depletion results in a complete collapse of the IMC that is lethal to the parasite. We demonstrate that localization of IMC32 is dependent on both an N-terminal palmitoylation site and a series of C-terminal coiled-coil domains. Using deletion analyses and functional complementation, we show that two conserved regions within the C-terminal coiled-coil domains play critical roles in protein function during replication. Together, this work reveals an essential component of parasite replication that provides a novel target for therapeutic intervention of T. gondii and related apicomplexan parasites.
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spelling pubmed-85451312021-10-27 Identification and Molecular Dissection of IMC32, a Conserved Toxoplasma Inner Membrane Complex Protein That Is Essential for Parasite Replication Torres, Juan A. Pasquarelli, Rebecca R. Back, Peter S. Moon, Andy S. Bradley, Peter J. mBio Research Article The inner membrane complex (IMC) is a unique organelle of apicomplexan parasites that plays critical roles in parasite motility, host cell invasion, and replication. Despite the common functions of the organelle, relatively few IMC proteins are conserved across the phylum and the precise roles of many IMC components remain to be characterized. Here, we identify a novel component of the Toxoplasma gondii IMC (IMC32) that localizes to the body portion of the IMC and is recruited to developing daughter buds early during endodyogeny. IMC32 is essential for parasite survival, as its conditional depletion results in a complete collapse of the IMC that is lethal to the parasite. We demonstrate that localization of IMC32 is dependent on both an N-terminal palmitoylation site and a series of C-terminal coiled-coil domains. Using deletion analyses and functional complementation, we show that two conserved regions within the C-terminal coiled-coil domains play critical roles in protein function during replication. Together, this work reveals an essential component of parasite replication that provides a novel target for therapeutic intervention of T. gondii and related apicomplexan parasites. American Society for Microbiology 2021-02-16 /pmc/articles/PMC8545131/ /pubmed/33593973 http://dx.doi.org/10.1128/mBio.03622-20 Text en Copyright © 2021 Torres et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Torres, Juan A.
Pasquarelli, Rebecca R.
Back, Peter S.
Moon, Andy S.
Bradley, Peter J.
Identification and Molecular Dissection of IMC32, a Conserved Toxoplasma Inner Membrane Complex Protein That Is Essential for Parasite Replication
title Identification and Molecular Dissection of IMC32, a Conserved Toxoplasma Inner Membrane Complex Protein That Is Essential for Parasite Replication
title_full Identification and Molecular Dissection of IMC32, a Conserved Toxoplasma Inner Membrane Complex Protein That Is Essential for Parasite Replication
title_fullStr Identification and Molecular Dissection of IMC32, a Conserved Toxoplasma Inner Membrane Complex Protein That Is Essential for Parasite Replication
title_full_unstemmed Identification and Molecular Dissection of IMC32, a Conserved Toxoplasma Inner Membrane Complex Protein That Is Essential for Parasite Replication
title_short Identification and Molecular Dissection of IMC32, a Conserved Toxoplasma Inner Membrane Complex Protein That Is Essential for Parasite Replication
title_sort identification and molecular dissection of imc32, a conserved toxoplasma inner membrane complex protein that is essential for parasite replication
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545131/
https://www.ncbi.nlm.nih.gov/pubmed/33593973
http://dx.doi.org/10.1128/mBio.03622-20
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