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Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites

Malaria remains a global driver of morbidity and mortality. To generate new antimalarials, one must elucidate the fundamental cell biology of Plasmodium falciparum, the parasite responsible for the deadliest cases of malaria. A membranous and proteinaceous scaffold called the inner membrane complex...

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Autores principales: Clements, Rebecca L., Morano, Alexander A., Navarro, Francesca M., McGee, James P., Du, Esrah W., Streva, Vincent A., Lindner, Scott E., Dvorin, Jeffrey D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9407223/
https://www.ncbi.nlm.nih.gov/pubmed/35972967
http://dx.doi.org/10.1073/pnas.2204167119
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author Clements, Rebecca L.
Morano, Alexander A.
Navarro, Francesca M.
McGee, James P.
Du, Esrah W.
Streva, Vincent A.
Lindner, Scott E.
Dvorin, Jeffrey D.
author_facet Clements, Rebecca L.
Morano, Alexander A.
Navarro, Francesca M.
McGee, James P.
Du, Esrah W.
Streva, Vincent A.
Lindner, Scott E.
Dvorin, Jeffrey D.
author_sort Clements, Rebecca L.
collection PubMed
description Malaria remains a global driver of morbidity and mortality. To generate new antimalarials, one must elucidate the fundamental cell biology of Plasmodium falciparum, the parasite responsible for the deadliest cases of malaria. A membranous and proteinaceous scaffold called the inner membrane complex (IMC) supports the parasite during morphological changes, including segmentation of daughter cells during asexual replication and formation of transmission-stage gametocytes. The basal complex lines the edge of the IMC during segmentation and likely facilitates IMC expansion. It is unknown, however, what drives IMC expansion during gametocytogenesis. We describe the discovery of a basal complex protein, PfBLEB, which we find to be essential for gametocytogenesis. Parasites lacking PfBLEB harbor defects in IMC expansion and are unable to form mature gametocytes. This article demonstrates a role for a basal complex protein outside of asexual division, and, importantly, highlights a potential molecular target for the ablation of malaria transmission.
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spelling pubmed-94072232023-02-16 Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites Clements, Rebecca L. Morano, Alexander A. Navarro, Francesca M. McGee, James P. Du, Esrah W. Streva, Vincent A. Lindner, Scott E. Dvorin, Jeffrey D. Proc Natl Acad Sci U S A Biological Sciences Malaria remains a global driver of morbidity and mortality. To generate new antimalarials, one must elucidate the fundamental cell biology of Plasmodium falciparum, the parasite responsible for the deadliest cases of malaria. A membranous and proteinaceous scaffold called the inner membrane complex (IMC) supports the parasite during morphological changes, including segmentation of daughter cells during asexual replication and formation of transmission-stage gametocytes. The basal complex lines the edge of the IMC during segmentation and likely facilitates IMC expansion. It is unknown, however, what drives IMC expansion during gametocytogenesis. We describe the discovery of a basal complex protein, PfBLEB, which we find to be essential for gametocytogenesis. Parasites lacking PfBLEB harbor defects in IMC expansion and are unable to form mature gametocytes. This article demonstrates a role for a basal complex protein outside of asexual division, and, importantly, highlights a potential molecular target for the ablation of malaria transmission. National Academy of Sciences 2022-08-16 2022-08-23 /pmc/articles/PMC9407223/ /pubmed/35972967 http://dx.doi.org/10.1073/pnas.2204167119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Clements, Rebecca L.
Morano, Alexander A.
Navarro, Francesca M.
McGee, James P.
Du, Esrah W.
Streva, Vincent A.
Lindner, Scott E.
Dvorin, Jeffrey D.
Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites
title Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites
title_full Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites
title_fullStr Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites
title_full_unstemmed Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites
title_short Identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites
title_sort identification of basal complex protein that is essential for maturation of transmission-stage malaria parasites
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9407223/
https://www.ncbi.nlm.nih.gov/pubmed/35972967
http://dx.doi.org/10.1073/pnas.2204167119
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