A central CRMP complex essential for invasion in Toxoplasma gondii

Apicomplexa are obligate intracellular parasites. While most species are restricted to specific hosts and cell types, Toxoplasma gondii can invade every nucleated cell derived from warm-blooded animals. This broad host range suggests that this parasite can recognize multiple host cell ligands or str...

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Main Authors: Mirko Singer, Kathrin Simon, Ignasi Forné, Markus Meissner
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2023-01-01
Series:PLoS Biology
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815656/?tool=EBI
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author Mirko Singer
Kathrin Simon
Ignasi Forné
Markus Meissner
author_facet Mirko Singer
Kathrin Simon
Ignasi Forné
Markus Meissner
author_sort Mirko Singer
collection DOAJ
description Apicomplexa are obligate intracellular parasites. While most species are restricted to specific hosts and cell types, Toxoplasma gondii can invade every nucleated cell derived from warm-blooded animals. This broad host range suggests that this parasite can recognize multiple host cell ligands or structures, leading to the activation of a central protein complex, which should be conserved in all apicomplexans. During invasion, the unique secretory organelles (micronemes and rhoptries) are sequentially released and several micronemal proteins have been suggested to be required for host cell recognition and invasion. However, to date, only few micronemal proteins have been demonstrated to be essential for invasion, suggesting functional redundancy that might allow such a broad host range. Cysteine Repeat Modular Proteins (CRMPs) are a family of apicomplexan-specific proteins. In T. gondii, two CRMPs are present in the genome, CRMPA (TGGT1_261080) and CRMPB (TGGT1_292020). Here, we demonstrate that both proteins form a complex that contains the additional proteins MIC15 and the thrombospondin type 1 domain-containing protein (TSP1). Disruption of this complex results in a block of rhoptry secretion and parasites being unable to invade the host cell. In conclusion, this complex is a central invasion complex conserved in all apicomplexans. This study identifies a novel protein complex containing a central CRMPA/CRMPB heterodimer with multiple transmembrane domains as being essential for host cell invasion by the apicomplexan parasite Toxoplasma gondii.
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spelling doaj.art-278cf1f0d4a74b5b829f00aaf7553d202023-01-08T05:30:28ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852023-01-01211A central CRMP complex essential for invasion in Toxoplasma gondiiMirko SingerKathrin SimonIgnasi FornéMarkus MeissnerApicomplexa are obligate intracellular parasites. While most species are restricted to specific hosts and cell types, Toxoplasma gondii can invade every nucleated cell derived from warm-blooded animals. This broad host range suggests that this parasite can recognize multiple host cell ligands or structures, leading to the activation of a central protein complex, which should be conserved in all apicomplexans. During invasion, the unique secretory organelles (micronemes and rhoptries) are sequentially released and several micronemal proteins have been suggested to be required for host cell recognition and invasion. However, to date, only few micronemal proteins have been demonstrated to be essential for invasion, suggesting functional redundancy that might allow such a broad host range. Cysteine Repeat Modular Proteins (CRMPs) are a family of apicomplexan-specific proteins. In T. gondii, two CRMPs are present in the genome, CRMPA (TGGT1_261080) and CRMPB (TGGT1_292020). Here, we demonstrate that both proteins form a complex that contains the additional proteins MIC15 and the thrombospondin type 1 domain-containing protein (TSP1). Disruption of this complex results in a block of rhoptry secretion and parasites being unable to invade the host cell. In conclusion, this complex is a central invasion complex conserved in all apicomplexans. This study identifies a novel protein complex containing a central CRMPA/CRMPB heterodimer with multiple transmembrane domains as being essential for host cell invasion by the apicomplexan parasite Toxoplasma gondii.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815656/?tool=EBI
spellingShingle Mirko Singer
Kathrin Simon
Ignasi Forné
Markus Meissner
A central CRMP complex essential for invasion in Toxoplasma gondii
PLoS Biology
title A central CRMP complex essential for invasion in Toxoplasma gondii
title_full A central CRMP complex essential for invasion in Toxoplasma gondii
title_fullStr A central CRMP complex essential for invasion in Toxoplasma gondii
title_full_unstemmed A central CRMP complex essential for invasion in Toxoplasma gondii
title_short A central CRMP complex essential for invasion in Toxoplasma gondii
title_sort central crmp complex essential for invasion in toxoplasma gondii
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815656/?tool=EBI
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