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 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.
Keywords
Asexual blood stage development, Plasmodium falciparum EPAC, AMA, PKA, cAMP-dependent protein kinase, Invasion adhesin apical membrane antigen 1, Malaria parasite host cell invasion machinery CyclicItem Type | Dataset |
---|---|
Capture method | Experiment |
Date | 10 May 2019 |
Language(s) of written materials | English |
Creator(s) |
Patel, A |
LSHTM Faculty/Department | Faculty of Infectious and Tropical Diseases |
Participating Institutions | London School of Hygiene & Tropical Medicine, London, United Kingdom |
Funders |
Project Funder Grant Number Funder URI |
Date Deposited | 18 Jul 2019 10:00 |
Last Modified | 08 Jul 2021 12:51 |
Publisher | PLoS Biology |
Explore Further
- Figshare (Data)
- Proteomecentral (Data)
- PLoS biology (Online Data Resource)
No files available. Please consult associated links.
- Figshare (Data)
- Proteomecentral (Data)
- PLoS biology (Online Data Resource)