The <italic toggle="yes">Toxoplasma</italic> Centrocone Houses Cell Cycle Regulatory Factors

ABSTRACT Our knowledge of cell cycle regulatory mechanisms in apicomplexan parasites is very limited. In this study, we describe a novel Toxoplasma gondii factor that has a vital role in chromosome replication and the regulation of cytoplasmic and nuclear mitotic structures, and we named this factor...

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Autores principales:	Anatoli Naumov, Stella Kratzer, Li-Min Ting, Kami Kim, Elena S. Suvorova, Michael W. White
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	E3 ligase Toxoplasma gondii apicomplexan parasites cell cycle chromosome replication cyclin-dependent kinases Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2ec5f4e3e56d40518266f7b5133f993f
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spelling	oai:doaj.org-article:2ec5f4e3e56d40518266f7b5133f993f2021-11-15T15:51:44ZThe <italic toggle="yes">Toxoplasma</italic> Centrocone Houses Cell Cycle Regulatory Factors10.1128/mBio.00579-172150-7511https://doaj.org/article/2ec5f4e3e56d40518266f7b5133f993f2017-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00579-17https://doaj.org/toc/2150-7511ABSTRACT Our knowledge of cell cycle regulatory mechanisms in apicomplexan parasites is very limited. In this study, we describe a novel Toxoplasma gondii factor that has a vital role in chromosome replication and the regulation of cytoplasmic and nuclear mitotic structures, and we named this factor ECR1 for essential for chromosome replication 1. ECR1 was discovered by complementation of a temperature-sensitive (ts) mutant that suffers lethal, uncontrolled chromosome replication at 40°C similar to a ts mutant carrying a defect in topoisomerase. ECR1 is a 52-kDa protein containing divergent RING and TRAF-Sina-like zinc binding domains that are dynamically expressed in the tachyzoite cell cycle. ECR1 first appears in the unique spindle compartment of the Apicomplexa (centrocone) of the nuclear envelope in early S phase and then in the nucleus in late S phase where it reaches maximum expression. Following nuclear division, but before daughter parasites separate from the mother parasite, ECR1 is downregulated and is absent in new daughter parasites. The proteomics of ECR1 identified interactions with the ubiquitin-mediated protein degradation machinery and the minichromosome maintenance complex, and the loss of ECR1 led to increased stability of a key member of this complex, MCM2. ECR1 also forms a stable complex with the cyclin-dependent kinase (CDK)-related kinase, T. gondii Crk5 (TgCrk5), which displays a similar cell cycle expression and localization during tachyzoite replication. Importantly, the localization of ECR1/TgCrk5 in the centrocone indicates that this Apicomplexa-specific spindle compartment houses important regulatory factors that control the parasite cell cycle. IMPORTANCE Parasites of the apicomplexan family are important causes of human disease, including malaria, toxoplasmosis, and cryptosporidiosis. Parasite growth is the underlying cause of pathogenesis, yet despite this importance, the molecular basis for parasite replication is poorly understood. Filling this knowledge gap cannot be accomplished by mining recent whole-genome sequencing data because apicomplexan cell cycles differ substantially and lack many of the key regulatory factors of well-studied yeast and mammalian cell division models. We have utilized forward genetics to discover essential factors that regulate cell division in these parasites using the Toxoplasma gondii model. An example of this approach is described here with the discovery of a putative E3 ligase/protein kinase mechanism involved in regulating chromosome replication and mitotic processes of asexual stage parasites.Anatoli NaumovStella KratzerLi-Min TingKami KimElena S. SuvorovaMichael W. WhiteAmerican Society for MicrobiologyarticleE3 ligaseToxoplasma gondiiapicomplexan parasitescell cyclechromosome replicationcyclin-dependent kinasesMicrobiologyQR1-502ENmBio, Vol 8, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	E3 ligase Toxoplasma gondii apicomplexan parasites cell cycle chromosome replication cyclin-dependent kinases Microbiology QR1-502
spellingShingle	E3 ligase Toxoplasma gondii apicomplexan parasites cell cycle chromosome replication cyclin-dependent kinases Microbiology QR1-502 Anatoli Naumov Stella Kratzer Li-Min Ting Kami Kim Elena S. Suvorova Michael W. White The <italic toggle="yes">Toxoplasma</italic> Centrocone Houses Cell Cycle Regulatory Factors
description	ABSTRACT Our knowledge of cell cycle regulatory mechanisms in apicomplexan parasites is very limited. In this study, we describe a novel Toxoplasma gondii factor that has a vital role in chromosome replication and the regulation of cytoplasmic and nuclear mitotic structures, and we named this factor ECR1 for essential for chromosome replication 1. ECR1 was discovered by complementation of a temperature-sensitive (ts) mutant that suffers lethal, uncontrolled chromosome replication at 40°C similar to a ts mutant carrying a defect in topoisomerase. ECR1 is a 52-kDa protein containing divergent RING and TRAF-Sina-like zinc binding domains that are dynamically expressed in the tachyzoite cell cycle. ECR1 first appears in the unique spindle compartment of the Apicomplexa (centrocone) of the nuclear envelope in early S phase and then in the nucleus in late S phase where it reaches maximum expression. Following nuclear division, but before daughter parasites separate from the mother parasite, ECR1 is downregulated and is absent in new daughter parasites. The proteomics of ECR1 identified interactions with the ubiquitin-mediated protein degradation machinery and the minichromosome maintenance complex, and the loss of ECR1 led to increased stability of a key member of this complex, MCM2. ECR1 also forms a stable complex with the cyclin-dependent kinase (CDK)-related kinase, T. gondii Crk5 (TgCrk5), which displays a similar cell cycle expression and localization during tachyzoite replication. Importantly, the localization of ECR1/TgCrk5 in the centrocone indicates that this Apicomplexa-specific spindle compartment houses important regulatory factors that control the parasite cell cycle. IMPORTANCE Parasites of the apicomplexan family are important causes of human disease, including malaria, toxoplasmosis, and cryptosporidiosis. Parasite growth is the underlying cause of pathogenesis, yet despite this importance, the molecular basis for parasite replication is poorly understood. Filling this knowledge gap cannot be accomplished by mining recent whole-genome sequencing data because apicomplexan cell cycles differ substantially and lack many of the key regulatory factors of well-studied yeast and mammalian cell division models. We have utilized forward genetics to discover essential factors that regulate cell division in these parasites using the Toxoplasma gondii model. An example of this approach is described here with the discovery of a putative E3 ligase/protein kinase mechanism involved in regulating chromosome replication and mitotic processes of asexual stage parasites.
format	article
author	Anatoli Naumov Stella Kratzer Li-Min Ting Kami Kim Elena S. Suvorova Michael W. White
author_facet	Anatoli Naumov Stella Kratzer Li-Min Ting Kami Kim Elena S. Suvorova Michael W. White
author_sort	Anatoli Naumov
title	The <italic toggle="yes">Toxoplasma</italic> Centrocone Houses Cell Cycle Regulatory Factors
title_short	The <italic toggle="yes">Toxoplasma</italic> Centrocone Houses Cell Cycle Regulatory Factors
title_full	The <italic toggle="yes">Toxoplasma</italic> Centrocone Houses Cell Cycle Regulatory Factors
title_fullStr	The <italic toggle="yes">Toxoplasma</italic> Centrocone Houses Cell Cycle Regulatory Factors
title_full_unstemmed	The <italic toggle="yes">Toxoplasma</italic> Centrocone Houses Cell Cycle Regulatory Factors
title_sort	<italic toggle="yes">toxoplasma</italic> centrocone houses cell cycle regulatory factors
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/2ec5f4e3e56d40518266f7b5133f993f
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The <italic toggle="yes">Toxoplasma</italic> Centrocone Houses Cell Cycle Regulatory Factors

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