Biagini, Giancarlo ORCID: https://orcid.org/0000-0001-6356-6595, Bray, Patrick, Spiller, D. G., White, M. R. H. and Ward, Stephen ORCID: https://orcid.org/0000-0003-2331-3192 (2003) 'The digestive food vacuole of the malaria parasite is a dynamic intracellular Ca2+ store'. Journal of Biological Chemistry, Vol 278, Issue 30, pp. 27910-27915.
Full text not available from this repository.Abstract
The acidic food vacuole of Plasmodium falciparum has been the subject of intense scientific investigation in the 40 years since its role in the digestion of host hemoglobin was first suggested. This proposed role has important implications for the complex host-parasite inter-relationship and also for the mode of action of several of the most effective antimalarial drugs. In addition, adaptive changes in the physiology of this organelle are implicated in drug resistance. Here we show that in addition to these functions, the digestive food vacuole of the malaria parasite is a dynamic internal store for free Ca2+, a role hitherto unsuspected. With the aid of live-cell laser scanning confocal imaging, spatio-temporal studies revealed that maintenance of elevated free Ca2+ in the digestive food vacuole (relative to cytosolic levels) is achieved by a thapsigargin (and cyclopiazonic acid)-sensitive Ca2+-pump in cooperation with a H+-dependent Ca2+ transporter. Redistribution of free cytosolic and vacuolar Ca2+ during parasite growth also suggests that vacuolar Ca2+ plays an essential role in parasite morphogenesis. These data imply that the digestive food vacuole of the malaria parasite is functionally akin to the vacuole of plants (tonoplast) and the small electron-dense granules of some parasites (acidocalcisomes) whereby H+-coupled Ca2+ transport is involved in ion transport, Ca2+ homeostasis, and signal transduction. These findings have significant implications for parasite development, antimalarial drug action, and mechanisms of drug resistance.
Item Type: | Article |
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Subjects: | QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified. QX Parasitology > Protozoa > QX 135 Plasmodia WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria |
Digital Object Identifer (DOI): | https://doi.org/10.1074/jbc.M304193200 |
Depositing User: | Martin Chapman |
Date Deposited: | 12 Feb 2013 11:00 |
Last Modified: | 22 Nov 2024 14:47 |
URI: | https://archive.lstmed.ac.uk/id/eprint/2501 |
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