Evidence against a Role of Elevated Intracellular Ca2+ during Plasmodium falciparum Preinvasion.
View / Open Files
Authors
Crick, Alex
Kotar, Jurij
Lin, Yen-Chun
Publication Date
2018-04-10Journal Title
Biophys J
ISSN
0006-3495
Publisher
Elsevier BV
Volume
114
Issue
7
Pages
1695-1706
Language
eng
Type
Article
This Version
AM
Physical Medium
Print
Metadata
Show full item recordCitation
Introini, V., Crick, A., Tiffert, T., Kotar, J., Lin, Y., Cicuta, P., & Lew, V. (2018). Evidence against a Role of Elevated Intracellular Ca2+ during Plasmodium falciparum Preinvasion.. Biophys J, 114 (7), 1695-1706. https://doi.org/10.1016/j.bpj.2018.02.023
Abstract
Severe malaria is primarily caused by Plasmodium falciparum parasites during their asexual reproduction cycle within red blood cells. One of the least understood stages in this cycle is the brief preinvasion period during which merozoite-red cell contacts lead to apical alignment of the merozoite in readiness for penetration, a stage of major relevance in the control of invasion efficiency. Red blood cell deformations associated with this process were suggested to be active plasma membrane responses mediated by transients of elevated intracellular calcium. Few studies have addressed this hypothesis because of technical challenges, and the results remained inconclusive. Here, Fluo-4 was used as a fluorescent calcium indicator with optimized protocols to investigate the distribution of the dye in red blood cell populations used as P. falciparum invasion targets in egress-invasion assays. Preinvasion dynamics was observed simultaneously under bright-field and fluorescence microscopy by recording egress-invasion events. All the egress-invasion sequences showed red blood cell deformations of varied intensities during the preinvasion period and the echinocytic changes that follow during invasion. Intraerythrocytic calcium signals were absent throughout this interval in over half the records and totally absent during the preinvasion period, regardless of deformation strength. When present, calcium signals were of a punctate modality, initiated within merozoites already poised for invasion. These results argue against a role of elevated intracellular calcium during the preinvasion stage. We suggest an alternative mechanism of merozoite-induced preinvasion deformations based on passive red cell responses to transient agonist-receptor interactions associated with the formation of adhesive coat filaments.
Keywords
Erythrocytes, Intracellular Space, Humans, Plasmodium falciparum, Calcium, Formaldehyde, Aniline Compounds, Pyruvic Acid, Xanthenes
Identifiers
External DOI: https://doi.org/10.1016/j.bpj.2018.02.023
This record's URL: https://www.repository.cam.ac.uk/handle/1810/275859
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: http://creativecommons.org/licenses/by-nc-nd/4.0/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.
Recommended or similar items
The following licence files are associated with this item: