Functional dissection of prenyltransferases reveals roles in endocytosis and secretory vacuolar sorting in type 2-ME49 strain of toxoplasma gondii DOI Creative Commons
Shaojun Long, Yuanfeng Wang, Jinghui Wang

et al.

Virulence, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Prenyltransferases act essential roles in the prenylation modification, which is significant for proteins, like small GTPases to execute various important activities Toxoplasma gondii (T.gondii). The structures and partial functions of prenyltransferases (FTase, GGTase-I, GGTase-II) process have been dissected T. gondii. However, cellular effects on type 2-ME49 strain are largely unknown. To address this gap, CRISPR/Cas9-based gene-editing technology was employed construct conditional knockdown strains ME49 strain. Subsequent observation ingestion ability host cytosolic molecules (e.g, green fluorescent protein [GFP]) status secretory vacuolar sorting post-knockdown revealed findings. Our study demonstrated that degradation FTase GGTase-II notably affected trafficking endocytic GFP rhoptry bulb. Additionally, depletion led disordered endoplasmic reticulum microtubules, as well impaired gliding motility. integrity mitochondrion damaged after GGTase-I. These findings underscore critical endocytosis gondii, thereby enhancing our understanding potential drug targets.

Language: Английский

Iron-mediated post-transcriptional regulation in Toxoplasma gondii DOI Creative Commons
Megan A. Sloan, Adam Scott, Dana Aghabi

et al.

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(2), P. e1012857 - e1012857

Published: Feb. 3, 2025

Iron is required to support almost all life; however, levels must be carefully regulated maintain homeostasis. Although the obligate parasite Toxoplasma gondii requires iron, how it responds upon iron limitation has not been investigated. Here, we show that depletion triggers significant transcriptional changes in parasite, including iron-dependent pathways. We find a subset of T. transcripts contain stem-loop structures, which have associated with post-transcriptional iron-mediated regulation other cellular systems. validate one these (found 3' UTR TGME49_261720) using reporter cell line. presence stem-loop-containing sufficient confer accumulation at transcript and protein under low iron. This response dose time-dependent specific for The likely driven by an increased mRNA stability Interestingly, around 400 genes. To examine potential mechanism this tested aconitase interaction found 43 enriched transcripts, but our UTR. However, endogenous led maintenance survival Our data demonstrate existence first time; suggests may important environments.

Language: Английский

Citations

1
The HCF101 protein is an important component of the cytosolic iron–sulfur synthesis pathway in Toxoplasma gondii DOI Creative Commons

Eléa A. Renaud,

Ambre J. M. Maupin,

Laurence Berry

et al.

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(2), P. e3003028 - e3003028

Published: Feb. 6, 2025

Several key cellular functions depend on proteins harboring an iron–sulfur (Fe-S) cofactor. As these Fe-S localize to several subcellular compartments, they require a dedicated machinery for cofactor assembly. For instance, in plants and algae there are cluster synthesis pathways localizing the cytosol, but also present mitochondrion chloroplast, 2 organelles of endosymbiotic origin. Toxoplasma gondii is plastid-bearing parasitic protist responsible pathology affecting humans other warm-blooded vertebrates. We have characterized homolog HCF101, originally identified as protein transferring clusters photosystem I subunits chloroplast. Contrarily plants, we shown that HCF101 does not plastid parasites, instead important component cytosolic assembly (CIA) pathway which vital . While CIA widely conserved eukaryotes, it first time involvement this pan-eukaryotic established. Moreover, essential parasite viability absent from its mammalian hosts, constitutes novel promising potential drug target.

Language: Английский

Citations

1
ZFT is the major iron and zinc transporter inToxoplasma gondii DOI Creative Commons
Dana Aghabi, Carmen Rubio,

Miguel Cortijo Martinez

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Abstract Transition metals, such as iron and zinc, are indispensable trace elements for eukaryotic life, acting co-factors in essential processes ranging from respiration metabolism to DNA replication. These metals can be transported into cells by an evolutionary-conserved family of metal transporters; however, how the ubiquitous mammalian parasite Toxoplasma gondii acquired has been unknown. Here, we have identified characterised first zinc importer T. . This transporter, named ZFT, localised plasma membrane is parasite’s life cycle. We find ZFT regulated availability overexpression sensitises excess zinc. Using a conditional knockdown system, that leads reduction mitochondrial switch more quiescent lifecycle stage. To confirm transport activity, parasite-associated iron, complements loss transporter activity yeast model. Overall, uptake demonstrated importance cell. finding reveals critical piece puzzle understanding this obligate intracellular thrives within its host.

Language: Английский

Citations

0
HCF101 is a novel component of the CIA cytosolic iron-sulfur synthesis pathway in the human pathogen Toxoplasma gondii DOI Creative Commons

Eléa A. Renaud,

Ambre J. M. Maupin,

Laurence Berry

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Abstract Several key cellular functions depend on proteins harboring an iron-sulfur (Fe-S) cofactor. As these Fe-S localize to several subcellular compartments, they require a dedicated machinery for cofactor assembly. For instance, in plants and algae there are cluster synthesis pathways localizing the cytosol, but also present mitochondrion chloroplast, two organelles of endosymbiotic origin. Toxoplasma gondii is plastid-bearing parasitic protist responsible pathology affecting humans other warm-blooded vertebrates. We have characterized homologue HCF101, originally identified as protein transferring clusters photosystem I subunits chloroplast. Contrarily plants, we shown that HCF101 does not plastid parasites, instead important component cytosolic assembly (CIA) pathway which vital . While CIA widely conserved eukaryotes, it first time involvement this pan-eukaryotic established. Moreover, essential parasite viability absent from its mammalian hosts, constitutes novel promising potential drug target.

Language: Английский

Citations

1
Iron‑sulfur cluster biogenesis and function in Apicomplexa parasites DOI

Eléa A. Renaud,

Ambre J. M. Maupin,

Sébastien Besteiro

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2024, Volume and Issue: 1872(1), P. 119876 - 119876

Published: Nov. 14, 2024

Language: Английский

Citations

1
Functional dissection of prenyltransferases reveals roles in endocytosis and secretory vacuolar sorting in type 2-ME49 strain of toxoplasma gondii DOI Creative Commons
Shaojun Long, Yuanfeng Wang, Jinghui Wang

et al.

Virulence, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Prenyltransferases act essential roles in the prenylation modification, which is significant for proteins, like small GTPases to execute various important activities Toxoplasma gondii (T.gondii). The structures and partial functions of prenyltransferases (FTase, GGTase-I, GGTase-II) process have been dissected T. gondii. However, cellular effects on type 2-ME49 strain are largely unknown. To address this gap, CRISPR/Cas9-based gene-editing technology was employed construct conditional knockdown strains ME49 strain. Subsequent observation ingestion ability host cytosolic molecules (e.g, green fluorescent protein [GFP]) status secretory vacuolar sorting post-knockdown revealed findings. Our study demonstrated that degradation FTase GGTase-II notably affected trafficking endocytic GFP rhoptry bulb. Additionally, depletion led disordered endoplasmic reticulum microtubules, as well impaired gliding motility. integrity mitochondrion damaged after GGTase-I. These findings underscore critical endocytosis gondii, thereby enhancing our understanding potential drug targets.

Language: Английский

Citations

0