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A plastid two-pore channel essential for inter-organelle communication and growth of Toxoplasma gondii
Two-pore channels (TPCs) are a ubiquitous family of cation channels that localize to acidic organelles in animals and plants to regulate numerous Ca(2+)-dependent events. Little is known about TPCs in unicellular organisms despite their ancient origins. Here, we characterize a TPC from Toxoplasma go...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490419/ https://www.ncbi.nlm.nih.gov/pubmed/34608145 http://dx.doi.org/10.1038/s41467-021-25987-5 |
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author | Li, Zhu-Hong King, Thayer P. Ayong, Lawrence Asady, Beejan Cai, Xinjiang Rahman, Taufiq Vella, Stephen A. Coppens, Isabelle Patel, Sandip Moreno, Silvia N. J. |
author_facet | Li, Zhu-Hong King, Thayer P. Ayong, Lawrence Asady, Beejan Cai, Xinjiang Rahman, Taufiq Vella, Stephen A. Coppens, Isabelle Patel, Sandip Moreno, Silvia N. J. |
author_sort | Li, Zhu-Hong |
collection | PubMed |
description | Two-pore channels (TPCs) are a ubiquitous family of cation channels that localize to acidic organelles in animals and plants to regulate numerous Ca(2+)-dependent events. Little is known about TPCs in unicellular organisms despite their ancient origins. Here, we characterize a TPC from Toxoplasma gondii, the causative agent of toxoplasmosis. TgTPC is a member of a novel clad of TPCs in Apicomplexa, distinct from previously identified TPCs and only present in coccidians. We show that TgTPC localizes not to acidic organelles but to the apicoplast, a non-photosynthetic plastid found in most apicomplexan parasites. Conditional silencing of TgTPC resulted in progressive loss of apicoplast integrity, severely affecting growth and the lytic cycle. Isolation of TPC null mutants revealed a selective role for TPCs in replication independent of apicoplast loss that required conserved residues within the pore-lining region. Using a genetically-encoded Ca(2+) indicator targeted to the apicoplast, we show that Ca(2+) signals deriving from the ER but not from the extracellular space are selectively transmitted to the lumen. Deletion of the TgTPC gene caused reduced apicoplast Ca(2+) uptake and membrane contact site formation between the apicoplast and the ER. Fundamental roles for TPCs in maintaining organelle integrity, inter-organelle communication and growth emerge. |
format | Online Article Text |
id | pubmed-8490419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84904192021-10-07 A plastid two-pore channel essential for inter-organelle communication and growth of Toxoplasma gondii Li, Zhu-Hong King, Thayer P. Ayong, Lawrence Asady, Beejan Cai, Xinjiang Rahman, Taufiq Vella, Stephen A. Coppens, Isabelle Patel, Sandip Moreno, Silvia N. J. Nat Commun Article Two-pore channels (TPCs) are a ubiquitous family of cation channels that localize to acidic organelles in animals and plants to regulate numerous Ca(2+)-dependent events. Little is known about TPCs in unicellular organisms despite their ancient origins. Here, we characterize a TPC from Toxoplasma gondii, the causative agent of toxoplasmosis. TgTPC is a member of a novel clad of TPCs in Apicomplexa, distinct from previously identified TPCs and only present in coccidians. We show that TgTPC localizes not to acidic organelles but to the apicoplast, a non-photosynthetic plastid found in most apicomplexan parasites. Conditional silencing of TgTPC resulted in progressive loss of apicoplast integrity, severely affecting growth and the lytic cycle. Isolation of TPC null mutants revealed a selective role for TPCs in replication independent of apicoplast loss that required conserved residues within the pore-lining region. Using a genetically-encoded Ca(2+) indicator targeted to the apicoplast, we show that Ca(2+) signals deriving from the ER but not from the extracellular space are selectively transmitted to the lumen. Deletion of the TgTPC gene caused reduced apicoplast Ca(2+) uptake and membrane contact site formation between the apicoplast and the ER. Fundamental roles for TPCs in maintaining organelle integrity, inter-organelle communication and growth emerge. Nature Publishing Group UK 2021-10-04 /pmc/articles/PMC8490419/ /pubmed/34608145 http://dx.doi.org/10.1038/s41467-021-25987-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Li, Zhu-Hong King, Thayer P. Ayong, Lawrence Asady, Beejan Cai, Xinjiang Rahman, Taufiq Vella, Stephen A. Coppens, Isabelle Patel, Sandip Moreno, Silvia N. J. A plastid two-pore channel essential for inter-organelle communication and growth of Toxoplasma gondii |
title | A plastid two-pore channel essential for inter-organelle communication and growth of Toxoplasma gondii |
title_full | A plastid two-pore channel essential for inter-organelle communication and growth of Toxoplasma gondii |
title_fullStr | A plastid two-pore channel essential for inter-organelle communication and growth of Toxoplasma gondii |
title_full_unstemmed | A plastid two-pore channel essential for inter-organelle communication and growth of Toxoplasma gondii |
title_short | A plastid two-pore channel essential for inter-organelle communication and growth of Toxoplasma gondii |
title_sort | plastid two-pore channel essential for inter-organelle communication and growth of toxoplasma gondii |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490419/ https://www.ncbi.nlm.nih.gov/pubmed/34608145 http://dx.doi.org/10.1038/s41467-021-25987-5 |
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