Role of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Protein GEXP07 in Maurer’s Cleft Morphology, Knob Architecture, and <named-content content-type="genus-species">P. falciparum</named-content> EMP1 Trafficking

ABSTRACT The malaria parasite Plasmodium falciparum traffics the virulence protein P. falciparum erythrocyte membrane protein 1 (PfEMP1) to the surface of infected red blood cells (RBCs) via membranous organelles, known as the Maurer’s clefts. We developed a method for efficient enrichment of Maurer...

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Autores principales:	Emma McHugh, Olivia M. S. Carmo, Adam Blanch, Oliver Looker, Boyin Liu, Snigdha Tiash, Dean Andrew, Steven Batinovic, Andy J. Y. Low, Hyun-Jung Cho, Paul McMillan, Leann Tilley, Matthew W. A. Dixon
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	malaria protein trafficking virulence determinants Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/039e9446a57547709d035256d1ed16e8
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spelling	oai:doaj.org-article:039e9446a57547709d035256d1ed16e82021-11-15T15:57:02ZRole of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Protein GEXP07 in Maurer’s Cleft Morphology, Knob Architecture, and <named-content content-type="genus-species">P. falciparum</named-content> EMP1 Trafficking10.1128/mBio.03320-192150-7511https://doaj.org/article/039e9446a57547709d035256d1ed16e82020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03320-19https://doaj.org/toc/2150-7511ABSTRACT The malaria parasite Plasmodium falciparum traffics the virulence protein P. falciparum erythrocyte membrane protein 1 (PfEMP1) to the surface of infected red blood cells (RBCs) via membranous organelles, known as the Maurer’s clefts. We developed a method for efficient enrichment of Maurer’s clefts and profiled the protein composition of this trafficking organelle. We identified 13 previously uncharacterized or poorly characterized Maurer’s cleft proteins. We generated transfectants expressing green fluorescent protein (GFP) fusions of 7 proteins and confirmed their Maurer’s cleft location. Using co-immunoprecipitation and mass spectrometry, we generated an interaction map of proteins at the Maurer’s clefts. We identified two key clusters that may function in the loading and unloading of PfEMP1 into and out of the Maurer’s clefts. We focus on a putative PfEMP1 loading complex that includes the protein GEXP07/CX3CL1-binding protein 2 (CBP2). Disruption of GEXP07 causes Maurer’s cleft fragmentation, aberrant knobs, ablation of PfEMP1 surface expression, and loss of the PfEMP1-mediated adhesion. ΔGEXP07 parasites have a growth advantage compared to wild-type parasites, and the infected RBCs are more deformable and more osmotically fragile. IMPORTANCE The trafficking of the virulence antigen PfEMP1 and its presentation at the knob structures at the surface of parasite-infected RBCs are central to severe adhesion-related pathologies such as cerebral and placental malaria. This work adds to our understanding of how PfEMP1 is trafficked to the RBC membrane by defining the protein-protein interaction networks that function at the Maurer’s clefts controlling PfEMP1 loading and unloading. We characterize a protein needed for virulence protein trafficking and provide new insights into the mechanisms for host cell remodeling, parasite survival within the host, and virulence.Emma McHughOlivia M. S. CarmoAdam BlanchOliver LookerBoyin LiuSnigdha TiashDean AndrewSteven BatinovicAndy J. Y. LowHyun-Jung ChoPaul McMillanLeann TilleyMatthew W. A. DixonAmerican Society for Microbiologyarticlemalariaprotein traffickingvirulence determinantsMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	malaria protein trafficking virulence determinants Microbiology QR1-502
spellingShingle	malaria protein trafficking virulence determinants Microbiology QR1-502 Emma McHugh Olivia M. S. Carmo Adam Blanch Oliver Looker Boyin Liu Snigdha Tiash Dean Andrew Steven Batinovic Andy J. Y. Low Hyun-Jung Cho Paul McMillan Leann Tilley Matthew W. A. Dixon Role of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Protein GEXP07 in Maurer’s Cleft Morphology, Knob Architecture, and <named-content content-type="genus-species">P. falciparum</named-content> EMP1 Trafficking
description	ABSTRACT The malaria parasite Plasmodium falciparum traffics the virulence protein P. falciparum erythrocyte membrane protein 1 (PfEMP1) to the surface of infected red blood cells (RBCs) via membranous organelles, known as the Maurer’s clefts. We developed a method for efficient enrichment of Maurer’s clefts and profiled the protein composition of this trafficking organelle. We identified 13 previously uncharacterized or poorly characterized Maurer’s cleft proteins. We generated transfectants expressing green fluorescent protein (GFP) fusions of 7 proteins and confirmed their Maurer’s cleft location. Using co-immunoprecipitation and mass spectrometry, we generated an interaction map of proteins at the Maurer’s clefts. We identified two key clusters that may function in the loading and unloading of PfEMP1 into and out of the Maurer’s clefts. We focus on a putative PfEMP1 loading complex that includes the protein GEXP07/CX3CL1-binding protein 2 (CBP2). Disruption of GEXP07 causes Maurer’s cleft fragmentation, aberrant knobs, ablation of PfEMP1 surface expression, and loss of the PfEMP1-mediated adhesion. ΔGEXP07 parasites have a growth advantage compared to wild-type parasites, and the infected RBCs are more deformable and more osmotically fragile. IMPORTANCE The trafficking of the virulence antigen PfEMP1 and its presentation at the knob structures at the surface of parasite-infected RBCs are central to severe adhesion-related pathologies such as cerebral and placental malaria. This work adds to our understanding of how PfEMP1 is trafficked to the RBC membrane by defining the protein-protein interaction networks that function at the Maurer’s clefts controlling PfEMP1 loading and unloading. We characterize a protein needed for virulence protein trafficking and provide new insights into the mechanisms for host cell remodeling, parasite survival within the host, and virulence.
format	article
author	Emma McHugh Olivia M. S. Carmo Adam Blanch Oliver Looker Boyin Liu Snigdha Tiash Dean Andrew Steven Batinovic Andy J. Y. Low Hyun-Jung Cho Paul McMillan Leann Tilley Matthew W. A. Dixon
author_facet	Emma McHugh Olivia M. S. Carmo Adam Blanch Oliver Looker Boyin Liu Snigdha Tiash Dean Andrew Steven Batinovic Andy J. Y. Low Hyun-Jung Cho Paul McMillan Leann Tilley Matthew W. A. Dixon
author_sort	Emma McHugh
title	Role of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Protein GEXP07 in Maurer’s Cleft Morphology, Knob Architecture, and <named-content content-type="genus-species">P. falciparum</named-content> EMP1 Trafficking
title_short	Role of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Protein GEXP07 in Maurer’s Cleft Morphology, Knob Architecture, and <named-content content-type="genus-species">P. falciparum</named-content> EMP1 Trafficking
title_full	Role of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Protein GEXP07 in Maurer’s Cleft Morphology, Knob Architecture, and <named-content content-type="genus-species">P. falciparum</named-content> EMP1 Trafficking
title_fullStr	Role of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Protein GEXP07 in Maurer’s Cleft Morphology, Knob Architecture, and <named-content content-type="genus-species">P. falciparum</named-content> EMP1 Trafficking
title_full_unstemmed	Role of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Protein GEXP07 in Maurer’s Cleft Morphology, Knob Architecture, and <named-content content-type="genus-species">P. falciparum</named-content> EMP1 Trafficking
title_sort	role of <named-content content-type="genus-species">plasmodium falciparum</named-content> protein gexp07 in maurer’s cleft morphology, knob architecture, and <named-content content-type="genus-species">p. falciparum</named-content> emp1 trafficking
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/039e9446a57547709d035256d1ed16e8
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Role of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Protein GEXP07 in Maurer’s Cleft Morphology, Knob Architecture, and <named-content content-type="genus-species">P. falciparum</named-content> EMP1 Trafficking

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