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...
Main Authors: | , , , |
---|---|
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 |
_version_ | 1797959117984235520 |
---|---|
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. |
first_indexed | 2024-04-11T00:29:12Z |
format | Article |
id | doaj.art-278cf1f0d4a74b5b829f00aaf7553d20 |
institution | Directory Open Access Journal |
issn | 1544-9173 1545-7885 |
language | English |
last_indexed | 2024-04-11T00:29:12Z |
publishDate | 2023-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS Biology |
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 |
work_keys_str_mv | AT mirkosinger acentralcrmpcomplexessentialforinvasionintoxoplasmagondii AT kathrinsimon acentralcrmpcomplexessentialforinvasionintoxoplasmagondii AT ignasiforne acentralcrmpcomplexessentialforinvasionintoxoplasmagondii AT markusmeissner acentralcrmpcomplexessentialforinvasionintoxoplasmagondii AT mirkosinger centralcrmpcomplexessentialforinvasionintoxoplasmagondii AT kathrinsimon centralcrmpcomplexessentialforinvasionintoxoplasmagondii AT ignasiforne centralcrmpcomplexessentialforinvasionintoxoplasmagondii AT markusmeissner centralcrmpcomplexessentialforinvasionintoxoplasmagondii |