Effects of Ca++ Depletion on the Asexual Cell Cycle of Plasmodium Falciparum

Wasserman, Moisés; Alarcón, Carmenza; Mendoza, Paula M.

doi:10.4269/ajtmh.1982.31.711

Cited by 89 publications

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“…3, f and g) producing "wagon wheel"-looking Ca 2ϩ distributions. It has been accepted for more than 20 years that Ca 2ϩ in the culture medium is essential for the complete asexual development of the malaria parasite in red blood cells in culture (23). The results presented here lend further support to a role for Ca 2ϩ -dependent processes in the asexual development of the parasite.…”

Section: Discussionsupporting

confidence: 70%

The Digestive Food Vacuole of the Malaria Parasite Is a Dynamic Intracellular Ca2+ Store

Biagini

Bray

Spiller

et al. 2003

Journal of Biological Chemistry

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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 Ca 2؉ , a role hitherto unsuspected. With the aid of live-cell laser scanning confocal imaging, spatiotemporal studies revealed that maintenance of elevated free Ca 2؉ in the digestive food vacuole (relative to cytosolic levels) is achieved by a thapsigargin (and cyclopiazonic acid)-sensitive Ca 2؉ -pump in cooperation with a H ؉ -dependent Ca 2؉ transporter. Redistribution of free cytosolic and vacuolar Ca 2؉ during parasite growth also suggests that vacuolar Ca 2؉ 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 Ca 2؉ transport is involved in ion transport, Ca 2؉ homeostasis, and signal transduction. These findings have significant implications for parasite development, antimalarial drug action, and mechanisms of drug resistance.Malaria remains one of the largest global health (and economic) problems, resulting in more than a million deaths, mostly in young African children (1). With this in mind, it is astonishing how little is known about the basic physiology of the intraerythrocytic malaria parasite and its organelles. The food vacuole is a major digestive organelle of the malaria parasite and a proven chemotherapeutic target. This organelle has a role in degradation of host-derived hemoglobin, is the site of action of important classes of antimalarials, and harbors transporters associated with drug resistance (2-4). Hydrolysis of hemoglobin in the malaria parasite digestive food vacuole occurs by the integrated action of aspartic, cysteine, and metalloproteases (5), resulting in the production of hemozoin (malaria pigment), a biocrystal of the toxic precursor ferriprotoporphyrin IX (FPIX) 1 (6). The internal pH of the digestive food vacuole is lower than the parasite cytosol, although the precise pH value is under debate (7). In collaboration with Prof. Kiaran Kirk's laboratory (8), we have recently described the function of two H ϩ -pumping mechanisms in the digestive food vacuole; one is a bafilomycin-sensitive V-type H ϩ -ATPase, and the other is a NaF-sensitive H ϩ -pyrophosphatase showing a partial dependence on K ϩ . The combination of a H ϩ -ATPase and a H ϩ -pyrophosphatase acting in the digestive vacuole is analogous to the situation in acidic tonoplasts of plant cells (9)...

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Section: Discussionsupporting

confidence: 70%

The Digestive Food Vacuole of the Malaria Parasite Is a Dynamic Intracellular Ca2+ Store

Biagini

Bray

Spiller

et al. 2003

Journal of Biological Chemistry

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“…El sistema calcio/calmodulina (CaM) cumple un papel muy importante en la maduración y la invasión del parásito al eritrocito (1); los estudios realizados en nuestro laboratorio indican que es necesaria una entrada transitoria de calcio para activar los eventos moleculares que conducen a la invasión (2). Se cree que el influjo de calcio en el glóbulo rojo puede activar a la CaM o a las PUCaM (proteínas de unión a calmodulina) y, en consecuencia, activar procesos regulados por el calcio relacionados con el crecimiento del parásito (3).…”

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Preparación de genotecas de ADNc de Plasmodium falciparum para la búsqueda de los genes de proteínas de unión a calmodulina, GOGAT y Pfmyo A.

Meza

Wasserman

2002

biomedica

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Se construyó una genoteca de ADNc representativa de los estadios asexuales de Plasmodium falciparum, en el vector λZipLox. Esta genoteca (de la cepa colombiana FCB2) y otra genoteca construida en λZAP II (de la cepa Dd2), se rastrearon en busca de genes de proteínas que se unen a calmodulina (CaM) o a proteínas relacionadas con CaM. Para el rastreo se usó tanto el ensayo de Hot-start PCR como la hibridización de filtros réplica con sondas radiomarcadas. Se identificaron clones de actina I, calmodulina (CaM), glutamato sintasa (GOGAT) y las tres miosinas Pfmyo A, Pfmyo B y Pfmyo C. Se aislaron clones para actina I, CaM y GOGAT en la genoteca construida en λZipLox y clones para GOGAT y Pfmyo A en la genoteca construida en λZAP II. Uno de los clones de GOGAT contiene un inserto de 2.413 pb que corresponde al 24,8% de la secuencia codificante informada. El inserto de Pfmyo A aislado tiene 2.457 pb y representa el mensajero completo del gen. La identidad de este inserto se confirmó mediante análisis de restricción. Este es el primer informe de un clon de ADNc completo de la miosina A de P. falciparum. Los clones aislados se utilizarán en estudios futuros, tales como la obtención de las proteínas recombinantes, producción de anticuerpos y ensayos de funcionalidad.Palabras clave: Plasmodium falciparum, malaria, proteína de unión a calmodulina, glutamato sintasa, miosina, ADNc. Screening for calmodulin, GOGAT and Pfmyo A genes in Plasmodium falciparum cDNA librariesA cDNA library of Plasmodium falciparum (Colombian strain FCB2) asexual stage was constructed in the λZipLox vector. The λZipLox library and a λZAPII (Dd2 strain) were screened for genes coding for proteins that bind with or are related to calmodulin (CaM). Screening was accomplished with Hot start PCR assays and hybridization with radiolabeled probes. Actin I, CaM, glutamate synthase (GOGAT) and the three myosin clones -Pfmyo A, Pfmyo B and Pfmyo C-were identified. The clones coding for actin I, CaM and GOGAT were retrieved from the λZipLox library, and the GOGAT and Pfmyo A clones from the λZAP II library. The GOGAT clone contained an insert of 2,413 base pairs corresponding to 24.8% of the reported sequence. The Pfmyo A insert was 2,457 base pairs long, and represented the complete mRNA coding for this gene. Finally, the first report of a complete cDNA clone containing the P. falciparum myosin A is presented.

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“…In our laboratory we have studied the role of calcium during invasion and we have shown that its depletion in the medium causes an inhibition of invasion partly due to the inability of the merozoite to reorientate and penetrate the erythrocytes (Wasserman et al 1982(Wasserman et al , 1990. It has been well established that calcium is an important mediator of assembly and disassembly of cytoskeleton (Bennet & Weeds 1986) and of molecular motors (Barkalow & Hartwig 1995, Wolenski 1995.…”

mentioning

confidence: 99%

Isolation and identification of actin-binding proteins in Plasmodium falciparum by affinity chromatography

Forero

Wasserman

2000

Mem. Inst. Oswaldo Cruz

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Effects of Ca++ Depletion on the Asexual Cell Cycle of Plasmodium Falciparum

Cited by 89 publications

References 0 publications

The Digestive Food Vacuole of the Malaria Parasite Is a Dynamic Intracellular Ca2+ Store

The Digestive Food Vacuole of the Malaria Parasite Is a Dynamic Intracellular Ca2+ Store

Preparación de genotecas de ADNc de Plasmodium falciparum para la búsqueda de los genes de proteínas de unión a calmodulina, GOGAT y Pfmyo A.

Isolation and identification of actin-binding proteins in Plasmodium falciparum by affinity chromatography

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