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Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery

Cyclic AMP (cAMP) is an important signalling molecule across evolution, but its role in malaria parasites is poorly understood. We have investigated the role of cAMP in asexual blood stage development of Plasmodium falciparum through conditional disruption of adenylyl cyclase beta (ACβ) and its down...

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Autores principales: Patel, Avnish, Perrin, Abigail J., Flynn, Helen R., Bisson, Claudine, Withers-Martinez, Chrislaine, Treeck, Moritz, Flueck, Christian, Nicastro, Giuseppe, Martin, Stephen R., Ramos, Andres, Gilberger, Tim W., Snijders, Ambrosius P., Blackman, Michael J., Baker, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530879/
https://www.ncbi.nlm.nih.gov/pubmed/31075098
http://dx.doi.org/10.1371/journal.pbio.3000264
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author Patel, Avnish
Perrin, Abigail J.
Flynn, Helen R.
Bisson, Claudine
Withers-Martinez, Chrislaine
Treeck, Moritz
Flueck, Christian
Nicastro, Giuseppe
Martin, Stephen R.
Ramos, Andres
Gilberger, Tim W.
Snijders, Ambrosius P.
Blackman, Michael J.
Baker, David A.
author_facet Patel, Avnish
Perrin, Abigail J.
Flynn, Helen R.
Bisson, Claudine
Withers-Martinez, Chrislaine
Treeck, Moritz
Flueck, Christian
Nicastro, Giuseppe
Martin, Stephen R.
Ramos, Andres
Gilberger, Tim W.
Snijders, Ambrosius P.
Blackman, Michael J.
Baker, David A.
author_sort Patel, Avnish
collection PubMed
description Cyclic AMP (cAMP) is an important signalling molecule across evolution, but its role in malaria parasites is poorly understood. We have investigated the role of cAMP in asexual blood stage development of Plasmodium falciparum through conditional disruption of adenylyl cyclase beta (ACβ) and its downstream effector, cAMP-dependent protein kinase (PKA). We show that both production of cAMP and activity of PKA are critical for erythrocyte invasion, whilst key developmental steps that precede invasion still take place in the absence of cAMP-dependent signalling. We also show that another parasite protein with putative cyclic nucleotide binding sites, Plasmodium falciparum EPAC (PfEpac), does not play an essential role in blood stages. We identify and quantify numerous sites, phosphorylation of which is dependent on cAMP signalling, and we provide mechanistic insight as to how cAMP-dependent phosphorylation of the cytoplasmic domain of the essential invasion adhesin apical membrane antigen 1 (AMA1) regulates erythrocyte invasion.
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spelling pubmed-65308792019-05-31 Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery Patel, Avnish Perrin, Abigail J. Flynn, Helen R. Bisson, Claudine Withers-Martinez, Chrislaine Treeck, Moritz Flueck, Christian Nicastro, Giuseppe Martin, Stephen R. Ramos, Andres Gilberger, Tim W. Snijders, Ambrosius P. Blackman, Michael J. Baker, David A. PLoS Biol Research Article Cyclic AMP (cAMP) is an important signalling molecule across evolution, but its role in malaria parasites is poorly understood. We have investigated the role of cAMP in asexual blood stage development of Plasmodium falciparum through conditional disruption of adenylyl cyclase beta (ACβ) and its downstream effector, cAMP-dependent protein kinase (PKA). We show that both production of cAMP and activity of PKA are critical for erythrocyte invasion, whilst key developmental steps that precede invasion still take place in the absence of cAMP-dependent signalling. We also show that another parasite protein with putative cyclic nucleotide binding sites, Plasmodium falciparum EPAC (PfEpac), does not play an essential role in blood stages. We identify and quantify numerous sites, phosphorylation of which is dependent on cAMP signalling, and we provide mechanistic insight as to how cAMP-dependent phosphorylation of the cytoplasmic domain of the essential invasion adhesin apical membrane antigen 1 (AMA1) regulates erythrocyte invasion. Public Library of Science 2019-05-10 /pmc/articles/PMC6530879/ /pubmed/31075098 http://dx.doi.org/10.1371/journal.pbio.3000264 Text en © 2019 Patel 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Patel, Avnish
Perrin, Abigail J.
Flynn, Helen R.
Bisson, Claudine
Withers-Martinez, Chrislaine
Treeck, Moritz
Flueck, Christian
Nicastro, Giuseppe
Martin, Stephen R.
Ramos, Andres
Gilberger, Tim W.
Snijders, Ambrosius P.
Blackman, Michael J.
Baker, David A.
Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery
title Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery
title_full Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery
title_fullStr Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery
title_full_unstemmed Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery
title_short Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery
title_sort cyclic amp signalling controls key components of malaria parasite host cell invasion machinery
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530879/
https://www.ncbi.nlm.nih.gov/pubmed/31075098
http://dx.doi.org/10.1371/journal.pbio.3000264
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