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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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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. |
format | Online Article Text |
id | pubmed-6530879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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