Organization and function of an actin cytoskeleton in<i>P</i><i>lasmodium falciparum</i>gametocytes

Hliscs, Marion; Millet, Coralie; Dixon, Matthew W. A.; Sidén‐Kiamos, Inga; McMillan, Paul J.; Tilley, Leann

doi:10.1111/cmi.12359

Cited by 57 publications

(63 citation statements)

References 82 publications

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“…It is known that gametocytes possess a trilaminar membrane structure subtended by a layer of structural microtubules that is reminiscent of that of invasive and motile stages (Angrisano et al., 2012, Sinden et al., 1978). It is also known that an F-actin cytoskeleton is concentrated at the ends of the elongating gametocyte, which extends inward along the microtubule cytoskeleton, and is still present in stage V gametocytes (Hliscs et al., 2015). Actin I is the major and ubiquitously expressed actin and is present in both male and female sexual stages, while actin II, a second conventional actin, is specifically expressed by the sexual stages (Deligianni et al., 2011, Rupp et al., 2011, Wesseling et al., 1989).…”

Section: Discussionmentioning

confidence: 99%

Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes

Bargieri

Thiberge

Tay

et al. 2016

Cell Host & Microbe

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SummarySurface-associated TRAP (thrombospondin-related anonymous protein) family proteins are conserved across the phylum of apicomplexan parasites. TRAP proteins are thought to play an integral role in parasite motility and cell invasion by linking the extracellular environment with the parasite submembrane actomyosin motor. Blood stage forms of the malaria parasite Plasmodium express a TRAP family protein called merozoite-TRAP (MTRAP) that has been implicated in erythrocyte invasion. Using MTRAP-deficient mutants of the rodent-infecting P. berghei and human-infecting P. falciparum parasites, we show that MTRAP is dispensable for erythrocyte invasion. Instead, MTRAP is essential for gamete egress from erythrocytes, where it is necessary for the disruption of the gamete-containing parasitophorous vacuole membrane, and thus for parasite transmission to mosquitoes. This indicates that motor-binding TRAP family members function not just in parasite motility and cell invasion but also in membrane disruption and cell egress.

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Section: Discussionmentioning

confidence: 99%

Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes

Bargieri

Thiberge

Tay

et al. 2016

Cell Host & Microbe

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“…S5A). It is important to note that these effects do not appear to result from compromised parasite viability, because we have previously shown that short-term cytochalasin treatment does not prevent gametocyte maturation (20).…”

Section: Chemical Modulation Of the Membrane Skeleton Enhancesmentioning

confidence: 97%

Reversible host cell remodeling underpins deformability changes in malaria parasite sexual blood stages

Dearnley

Chu

Zhang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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101

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The sexual blood stage of the human malaria parasite Plasmodium falciparum undergoes remarkable biophysical changes as it prepares for transmission to mosquitoes. During maturation, midstage gametocytes show low deformability and sequester in the bone marrow and spleen cords, thus avoiding clearance during passage through splenic sinuses. Mature gametocytes exhibit increased deformability and reappear in the peripheral circulation, allowing uptake by mosquitoes. Here we define the reversible changes in erythrocyte membrane organization that underpin this biomechanical transformation. Atomic force microscopy reveals that the length of the spectrin crossmembers and the size of the skeletal meshwork increase in developing gametocytes, then decrease in mature-stage gametocytes. These changes are accompanied by relocation of actin from the erythrocyte membrane to the Maurer's clefts. Fluorescence recovery after photobleaching reveals reversible changes in the level of coupling between the membrane skeleton and the plasma membrane. Treatment of midstage gametocytes with cytochalasin D decreases the vertical coupling and increases their filterability. A computationally efficient coarse-grained model of the erythrocyte membrane reveals that restructuring and constraining the spectrin meshwork can fully account for the observed changes in deformability.gametocyte | deformability | spectrin/actin skeleton | AFM | molecular dynamics simulation T he most virulent of the human malaria parasites, Plasmodium falciparum causes ∼440,000 deaths annually (1). Pathology is associated with asexual multiplication within red blood cells (RBCs). The trophozoite (growing) and schizont (dividing) stages (∼24-48 h after invasion) sequester in deep tissue using adhesive proteins presented on platform-like structures called "knobs" at the infected RBC surface. Cytoadhesion enables the parasite to avoid passage through the splenic sinuses and thus mechanical clearance from the circulation. Unfortunately, complications associated with sequestration of infected RBCs in the brain are responsible for much of the malaria-related mortality and morbidity.After a period of asexual cycling, a proportion of blood-stage parasites commit to sexual development (gametocytogenesis). The intraerythrocytic gametocyte develops through five distinct stages (I-V) over a period of 10-12 d, eventually adopting the characteristic crescent (falciform) shape that gives P. falciparum its name. Elongation is driven by assembly of a sheath of microtubules, attached to an inner membrane complex, underneath the parasite plasma membrane. From stage II to IV, gametocytes disappear from the circulation (2, 3); however, the mechanism of sequestration is not well understood. Upon maturation, the microtubule cytoskeleton is disassembled, and stage V gametocytes re-enter the circulation (2, 3). Ingestion of mature gametocytes by an Anopheles mosquito triggers release from the RBCs, followed by sexual recombination in the insect gut, and eventual transmission.

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“…This raises concerns about previous studies of actin polymerization kinetics based on mis-folded actin. Furthermore, imaging studies on different life cycle stages of the apicomplexan parasite, Plasmodium falciparum, demonstrated the formation of an extensive F-actin cytoskeleton in both gametocytes and ookinetes (Hliscs et al, 2015; Siden-Kiamos et al, 2012). Using 3D-SIM it was demonstrated in gametocytes that these filaments appear to be organized in the cytoplasm, below the Inner Membrane Complex (IMC; a specialised structure found in apicomplexans that consists of membranous vesicles and structural components located just beneath the plasma membrane) of the parasite rather than between the IMC and the plasma membrane (Hliscs et al, 2015), where it is thought to power parasite gliding motility (Meissner et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Toxoplasma gondii F-actin forms an extensive filamentous network required for material exchange and parasite maturation

Periz

Whitelaw

Harding

et al. 2017

eLife

106

188

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Apicomplexan actin is important during the parasite's life cycle. Its polymerization kinetics are unusual, permitting only short, unstable F-actin filaments. It has not been possible to study actin in vivo and so its physiological roles have remained obscure, leading to models distinct from conventional actin behaviour. Here a modified version of the commercially available actin-chromobody was tested as a novel tool for visualising F-actin dynamics in Toxoplasma gondii. Cb labels filamentous actin structures within the parasite cytosol and labels an extensive F-actin network that connects parasites within the parasitophorous vacuole and allows vesicles to be exchanged between parasites. In the absence of actin, parasites lack a residual body and inter-parasite connections and grow in an asynchronous and disorganized manner. Collectively, these data identify new roles for actin in the intracellular phase of the parasites lytic cycle and provide a robust new tool for imaging parasitic F-actin dynamics.DOI: http://dx.doi.org/10.7554/eLife.24119.001

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Organization and function of an actin cytoskeleton inPlasmodium falciparumgametocytes

Cited by 57 publications

References 82 publications

Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes

Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes

Reversible host cell remodeling underpins deformability changes in malaria parasite sexual blood stages

Toxoplasma gondii F-actin forms an extensive filamentous network required for material exchange and parasite maturation

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