Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite

ABSTRACT Merozoites formed after asexual division of the malaria parasite invade the host red blood cells (RBCs), which is critical for initiating malaria infection. The process of invasion involves specialized organelles like micronemes and rhoptries that discharge key proteins involved in interact...

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Autores principales:	Roseleen Ekka, Ankit Gupta, Sonika Bhatnagar, Pawan Malhotra, Pushkar Sharma
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	phosphorylation malaria signaling invasion host cell invasion protein phosphorylation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d8262729f37a4593898a498999d4be28
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spelling	oai:doaj.org-article:d8262729f37a4593898a498999d4be282021-11-15T16:19:08ZPhosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite10.1128/mBio.00166-202150-7511https://doaj.org/article/d8262729f37a4593898a498999d4be282020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00166-20https://doaj.org/toc/2150-7511ABSTRACT Merozoites formed after asexual division of the malaria parasite invade the host red blood cells (RBCs), which is critical for initiating malaria infection. The process of invasion involves specialized organelles like micronemes and rhoptries that discharge key proteins involved in interaction with host RBC receptors. RhopH complex comprises at least three proteins, which include RhopH3. RhopH3 is critical for the process of red blood cell (RBC) invasion as well as intraerythrocytic development of human malaria parasite Plasmodium falciparum. It is phosphorylated at serine 804 (S804) in the parasite; however, it is unclear if phosphorylation regulates its function. To address this, a CRISPR-CAS9-based approach was used to mutate S804 to alanine (A) in P. falciparum. Using this phosphomutant (R3_S804A) of RhopH3, we demonstrate that the phosphorylation of S804 is critical for host RBC invasion by the parasite but not for its intraerythrocytic development. Importantly, the phosphorylation of RhopH3 regulates its localization to the rhoptries and discharge from the parasite, which is critical for RBC invasion. We also identified P. falciparum CDPK1 (PfCDPK1) as a possible candidate kinase for RhopH3-S804 phosphorylation and found that it regulates RhopH3 secretion from the parasite. These findings provide novel insights into the role of phosphorylation in rhoptry release and invasion, which is poorly understood. IMPORTANCE Host cell invasion by the malaria parasite is critical for establishing infection in human host and is dependent on discharge of key ligands from organelles like rhoptry and microneme, and these ligands interact with host RBC receptors. In the present study, we demonstrate that phosphorylation of a key rhoptry protein, RhopH3, is critical for host invasion. Phosphorylation regulates its localization to rhoptries and discharge from the parasite.Roseleen EkkaAnkit GuptaSonika BhatnagarPawan MalhotraPushkar SharmaAmerican Society for Microbiologyarticlephosphorylationmalariasignalinginvasionhost cell invasionprotein phosphorylationMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	phosphorylation malaria signaling invasion host cell invasion protein phosphorylation Microbiology QR1-502
spellingShingle	phosphorylation malaria signaling invasion host cell invasion protein phosphorylation Microbiology QR1-502 Roseleen Ekka Ankit Gupta Sonika Bhatnagar Pawan Malhotra Pushkar Sharma Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite
description	ABSTRACT Merozoites formed after asexual division of the malaria parasite invade the host red blood cells (RBCs), which is critical for initiating malaria infection. The process of invasion involves specialized organelles like micronemes and rhoptries that discharge key proteins involved in interaction with host RBC receptors. RhopH complex comprises at least three proteins, which include RhopH3. RhopH3 is critical for the process of red blood cell (RBC) invasion as well as intraerythrocytic development of human malaria parasite Plasmodium falciparum. It is phosphorylated at serine 804 (S804) in the parasite; however, it is unclear if phosphorylation regulates its function. To address this, a CRISPR-CAS9-based approach was used to mutate S804 to alanine (A) in P. falciparum. Using this phosphomutant (R3_S804A) of RhopH3, we demonstrate that the phosphorylation of S804 is critical for host RBC invasion by the parasite but not for its intraerythrocytic development. Importantly, the phosphorylation of RhopH3 regulates its localization to the rhoptries and discharge from the parasite, which is critical for RBC invasion. We also identified P. falciparum CDPK1 (PfCDPK1) as a possible candidate kinase for RhopH3-S804 phosphorylation and found that it regulates RhopH3 secretion from the parasite. These findings provide novel insights into the role of phosphorylation in rhoptry release and invasion, which is poorly understood. IMPORTANCE Host cell invasion by the malaria parasite is critical for establishing infection in human host and is dependent on discharge of key ligands from organelles like rhoptry and microneme, and these ligands interact with host RBC receptors. In the present study, we demonstrate that phosphorylation of a key rhoptry protein, RhopH3, is critical for host invasion. Phosphorylation regulates its localization to rhoptries and discharge from the parasite.
format	article
author	Roseleen Ekka Ankit Gupta Sonika Bhatnagar Pawan Malhotra Pushkar Sharma
author_facet	Roseleen Ekka Ankit Gupta Sonika Bhatnagar Pawan Malhotra Pushkar Sharma
author_sort	Roseleen Ekka
title	Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite
title_short	Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite
title_full	Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite
title_fullStr	Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite
title_full_unstemmed	Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite
title_sort	phosphorylation of rhoptry protein rhoph3 is critical for host cell invasion by the malaria parasite
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/d8262729f37a4593898a498999d4be28
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Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite

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