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Evidence that the Plasmodium falciparum Protein Sortilin Potentially Acts as an Escorter for the Trafficking of the Rhoptry-Associated Membrane Antigen to the Rhoptries

The rhoptry organelle is critical for the invasion of an erythrocyte by the malaria parasite Plasmodium falciparum. Despite their critical roles, the mechanisms behind their biogenesis are still poorly defined. Our earlier work had suggested that the interaction between the glycosylphosphatidylinosi...

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Autores principales: Hallée, Stéphanie, Boddey, Justin A., Cowman, Alan F., Richard, Dave
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750388/
https://www.ncbi.nlm.nih.gov/pubmed/29299530
http://dx.doi.org/10.1128/mSphere.00551-17
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author Hallée, Stéphanie
Boddey, Justin A.
Cowman, Alan F.
Richard, Dave
author_facet Hallée, Stéphanie
Boddey, Justin A.
Cowman, Alan F.
Richard, Dave
author_sort Hallée, Stéphanie
collection PubMed
description The rhoptry organelle is critical for the invasion of an erythrocyte by the malaria parasite Plasmodium falciparum. Despite their critical roles, the mechanisms behind their biogenesis are still poorly defined. Our earlier work had suggested that the interaction between the glycosylphosphatidylinositol (GPI)-anchored rhoptry-associated membrane antigen (RAMA) and the soluble rhoptry-associated protein 1 was involved in the transport of the latter from the Golgi apparatus to the rhoptry. However, how this protein complex could interact with the intracellular trafficking machinery was unknown at this stage. Here we show that the P. falciparum homologue of the transmembrane protein sortilin-VPS10 interacts with regions of RAMA that are sufficient to target a fluorescent reporter to the rhoptries. These results suggest that P. falciparum sortilin (PfSortilin) could potentially act as the escorter for the transport of rhoptry-destined cargo. IMPORTANCE The malaria parasite is a massive burden in several parts of the world. Worryingly, the parasite has become resistant to several of the drugs commonly used to treat the disease, and at this time, there is no commercial vaccine. It is therefore critical to identify new targets for the development of antimalarials. To survive in the human body, the malaria parasite needs to invade red blood cells. For this, it uses a variety of effectors stored in organelles forming a structure called the apical complex. The mechanisms behind how the parasite generates the apical complex are poorly understood. In this study, we present evidence that a transmembrane protein called sortilin potentially acts as an escorter to transport proteins from the Golgi apparatus to the rhoptries, a component of the apical complex. Our study provides new insight into the biogenesis of a critical structure of the malaria parasite.
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spelling pubmed-57503882018-01-03 Evidence that the Plasmodium falciparum Protein Sortilin Potentially Acts as an Escorter for the Trafficking of the Rhoptry-Associated Membrane Antigen to the Rhoptries Hallée, Stéphanie Boddey, Justin A. Cowman, Alan F. Richard, Dave mSphere Research Article The rhoptry organelle is critical for the invasion of an erythrocyte by the malaria parasite Plasmodium falciparum. Despite their critical roles, the mechanisms behind their biogenesis are still poorly defined. Our earlier work had suggested that the interaction between the glycosylphosphatidylinositol (GPI)-anchored rhoptry-associated membrane antigen (RAMA) and the soluble rhoptry-associated protein 1 was involved in the transport of the latter from the Golgi apparatus to the rhoptry. However, how this protein complex could interact with the intracellular trafficking machinery was unknown at this stage. Here we show that the P. falciparum homologue of the transmembrane protein sortilin-VPS10 interacts with regions of RAMA that are sufficient to target a fluorescent reporter to the rhoptries. These results suggest that P. falciparum sortilin (PfSortilin) could potentially act as the escorter for the transport of rhoptry-destined cargo. IMPORTANCE The malaria parasite is a massive burden in several parts of the world. Worryingly, the parasite has become resistant to several of the drugs commonly used to treat the disease, and at this time, there is no commercial vaccine. It is therefore critical to identify new targets for the development of antimalarials. To survive in the human body, the malaria parasite needs to invade red blood cells. For this, it uses a variety of effectors stored in organelles forming a structure called the apical complex. The mechanisms behind how the parasite generates the apical complex are poorly understood. In this study, we present evidence that a transmembrane protein called sortilin potentially acts as an escorter to transport proteins from the Golgi apparatus to the rhoptries, a component of the apical complex. Our study provides new insight into the biogenesis of a critical structure of the malaria parasite. American Society for Microbiology 2018-01-03 /pmc/articles/PMC5750388/ /pubmed/29299530 http://dx.doi.org/10.1128/mSphere.00551-17 Text en Copyright © 2018 Hallée et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Hallée, Stéphanie
Boddey, Justin A.
Cowman, Alan F.
Richard, Dave
Evidence that the Plasmodium falciparum Protein Sortilin Potentially Acts as an Escorter for the Trafficking of the Rhoptry-Associated Membrane Antigen to the Rhoptries
title Evidence that the Plasmodium falciparum Protein Sortilin Potentially Acts as an Escorter for the Trafficking of the Rhoptry-Associated Membrane Antigen to the Rhoptries
title_full Evidence that the Plasmodium falciparum Protein Sortilin Potentially Acts as an Escorter for the Trafficking of the Rhoptry-Associated Membrane Antigen to the Rhoptries
title_fullStr Evidence that the Plasmodium falciparum Protein Sortilin Potentially Acts as an Escorter for the Trafficking of the Rhoptry-Associated Membrane Antigen to the Rhoptries
title_full_unstemmed Evidence that the Plasmodium falciparum Protein Sortilin Potentially Acts as an Escorter for the Trafficking of the Rhoptry-Associated Membrane Antigen to the Rhoptries
title_short Evidence that the Plasmodium falciparum Protein Sortilin Potentially Acts as an Escorter for the Trafficking of the Rhoptry-Associated Membrane Antigen to the Rhoptries
title_sort evidence that the plasmodium falciparum protein sortilin potentially acts as an escorter for the trafficking of the rhoptry-associated membrane antigen to the rhoptries
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750388/
https://www.ncbi.nlm.nih.gov/pubmed/29299530
http://dx.doi.org/10.1128/mSphere.00551-17
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