Translocation of Dense Granule Effectors across the Parasitophorous Vacuole Membrane in Toxoplasma- Infected Cells Requires the Activity of ROP17, a Rhoptry Protein Kinase

MSphere
Michael W PanasJohn C Boothroyd

Abstract

Toxoplasma gondii tachyzoites co-opt host cell functions through introduction of a large set of rhoptry- and dense granule-derived effector proteins. These effectors reach the host cytosol through different means: direct injection for rhoptry effectors and translocation across the parasitophorous vacuolar membrane (PVM) for dense granule (GRA) effectors. The machinery that translocates these GRA effectors has recently been partially elucidated, revealing three components, MYR1, MYR2, and MYR3. To determine whether other proteins might be involved, we returned to a library of mutants defective in GRA translocation and selected one with a partial defect, suggesting it might be in a gene encoding a new component of the machinery. Surprisingly, whole-genome sequencing revealed a missense mutation in a gene encoding a known rhoptry protein, a serine/threonine protein kinase known as ROP17. ROP17 resides on the host cytosol side of the PVM in infected cells and has previously been known for its activity in phosphorylating and thereby inactivating host immunity-related GTPases. Here, we show that null or catalytically dead mutants of ROP17 are defective in GRA translocation across the PVM but that translocation can be rescued "in tran...Continue Reading

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Citations

Jul 19, 2020·Annual Review of Microbiology·Yifan WangJeroen P J Saeij
Oct 2, 2019·Frontiers in Cellular and Infection Microbiology·Tatiana Paredes-SantosJeroen P Saeij
Jun 26, 2020·MSphere·Michael W Panas, John C Boothroyd
Jan 6, 2021·Molecular Microbiology·Michael W Panas, John C Boothroyd
Feb 14, 2021·International Journal for Parasitology·Rajshekhar Y GajiAnne M Brown
Apr 2, 2021·PLoS Pathogens·Josh R Beck, Chi-Min Ho
Apr 28, 2021·Parasitology International·Fumiaki Ihara, Yoshifumi Nishikawa
Jun 29, 2021·Folia Parasitologica·Min GuoHai-Long Wang

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Datasets Mentioned

BETA
GSE133144
GSE122786

Methods Mentioned

BETA
GTPases
fluorescence-activated cell sorting
PCR
RNASeq
scraping
transfections
transfection
PCA

Software Mentioned

GSEA
GATK
Prism
RNASeq
CLC Genomics Workbench
SnpEff
picard
bowtie2
samtools mpileup
ImageJ

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