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Protein Kinase A Dependent Phosphorylation of Apical Membrane Antigen 1 Plays an Important Role in Erythrocyte Invasion by the Malaria Parasite

Apicomplexan parasites are obligate intracellular parasites that infect a variety of hosts, causing significant diseases in livestock and humans. The invasive forms of the parasites invade their host cells by gliding motility, an active process driven by parasite adhesion proteins and molecular moto...

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Autores principales: Leykauf, Kerstin, Treeck, Moritz, Gilson, Paul R., Nebl, Thomas, Braulke, Thomas, Cowman, Alan F., Gilberger, Tim W., Crabb, Brendan S.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880582/
https://www.ncbi.nlm.nih.gov/pubmed/20532217
http://dx.doi.org/10.1371/journal.ppat.1000941
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author Leykauf, Kerstin
Treeck, Moritz
Gilson, Paul R.
Nebl, Thomas
Braulke, Thomas
Cowman, Alan F.
Gilberger, Tim W.
Crabb, Brendan S.
author_facet Leykauf, Kerstin
Treeck, Moritz
Gilson, Paul R.
Nebl, Thomas
Braulke, Thomas
Cowman, Alan F.
Gilberger, Tim W.
Crabb, Brendan S.
author_sort Leykauf, Kerstin
collection PubMed
description Apicomplexan parasites are obligate intracellular parasites that infect a variety of hosts, causing significant diseases in livestock and humans. The invasive forms of the parasites invade their host cells by gliding motility, an active process driven by parasite adhesion proteins and molecular motors. A crucial point during host cell invasion is the formation of a ring-shaped area of intimate contact between the parasite and the host known as a tight junction. As the invasive zoite propels itself into the host-cell, the junction moves down the length of the parasite. This process must be tightly regulated and signalling is likely to play a role in this event. One crucial protein for tight-junction formation is the apical membrane antigen 1 (AMA1). Here we have investigated the phosphorylation status of this key player in the invasion process in the human malaria parasite Plasmodium falciparum. We show that the cytoplasmic tail of P. falciparum AMA1 is phosphorylated at serine 610. We provide evidence that the enzyme responsible for serine 610 phosphorylation is the cAMP regulated protein kinase A (PfPKA). Importantly, mutation of AMA1 serine 610 to alanine abrogates phosphorylation of AMA1 in vivo and dramatically impedes invasion. In addition to shedding unexpected new light on AMA1 function, this work represents the first time PKA has been implicated in merozoite invasion.
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spelling pubmed-28805822010-06-07 Protein Kinase A Dependent Phosphorylation of Apical Membrane Antigen 1 Plays an Important Role in Erythrocyte Invasion by the Malaria Parasite Leykauf, Kerstin Treeck, Moritz Gilson, Paul R. Nebl, Thomas Braulke, Thomas Cowman, Alan F. Gilberger, Tim W. Crabb, Brendan S. PLoS Pathog Research Article Apicomplexan parasites are obligate intracellular parasites that infect a variety of hosts, causing significant diseases in livestock and humans. The invasive forms of the parasites invade their host cells by gliding motility, an active process driven by parasite adhesion proteins and molecular motors. A crucial point during host cell invasion is the formation of a ring-shaped area of intimate contact between the parasite and the host known as a tight junction. As the invasive zoite propels itself into the host-cell, the junction moves down the length of the parasite. This process must be tightly regulated and signalling is likely to play a role in this event. One crucial protein for tight-junction formation is the apical membrane antigen 1 (AMA1). Here we have investigated the phosphorylation status of this key player in the invasion process in the human malaria parasite Plasmodium falciparum. We show that the cytoplasmic tail of P. falciparum AMA1 is phosphorylated at serine 610. We provide evidence that the enzyme responsible for serine 610 phosphorylation is the cAMP regulated protein kinase A (PfPKA). Importantly, mutation of AMA1 serine 610 to alanine abrogates phosphorylation of AMA1 in vivo and dramatically impedes invasion. In addition to shedding unexpected new light on AMA1 function, this work represents the first time PKA has been implicated in merozoite invasion. Public Library of Science 2010-06-03 /pmc/articles/PMC2880582/ /pubmed/20532217 http://dx.doi.org/10.1371/journal.ppat.1000941 Text en Leykauf et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Leykauf, Kerstin
Treeck, Moritz
Gilson, Paul R.
Nebl, Thomas
Braulke, Thomas
Cowman, Alan F.
Gilberger, Tim W.
Crabb, Brendan S.
Protein Kinase A Dependent Phosphorylation of Apical Membrane Antigen 1 Plays an Important Role in Erythrocyte Invasion by the Malaria Parasite
title Protein Kinase A Dependent Phosphorylation of Apical Membrane Antigen 1 Plays an Important Role in Erythrocyte Invasion by the Malaria Parasite
title_full Protein Kinase A Dependent Phosphorylation of Apical Membrane Antigen 1 Plays an Important Role in Erythrocyte Invasion by the Malaria Parasite
title_fullStr Protein Kinase A Dependent Phosphorylation of Apical Membrane Antigen 1 Plays an Important Role in Erythrocyte Invasion by the Malaria Parasite
title_full_unstemmed Protein Kinase A Dependent Phosphorylation of Apical Membrane Antigen 1 Plays an Important Role in Erythrocyte Invasion by the Malaria Parasite
title_short Protein Kinase A Dependent Phosphorylation of Apical Membrane Antigen 1 Plays an Important Role in Erythrocyte Invasion by the Malaria Parasite
title_sort protein kinase a dependent phosphorylation of apical membrane antigen 1 plays an important role in erythrocyte invasion by the malaria parasite
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880582/
https://www.ncbi.nlm.nih.gov/pubmed/20532217
http://dx.doi.org/10.1371/journal.ppat.1000941
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