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Calcium signaling in a low calcium environment: how the intracellular malaria parasite solves the problem.

Gazarini ML, Thomas AP, Pozzan T, Garcia CR - J. Cell Biol. (2003)

Bottom Line: This allowed selective loading of the Ca2+ probes within the PV.The [Ca2+] within this compartment was found to be approximately 40 microM, i.e., high enough to be compatible with a normal loading of the Plasmodia intracellular Ca2+ stores, a prerequisite for the use of a Ca2+-based signaling mechanism.We also show that reduction of extracellular [Ca2+] results in a slow depletion of the [Ca2+] within the PV.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo 05508-900, Brazil.

ABSTRACT
Malaria parasites, Plasmodia, spend most of their asexual life cycle within red blood cells, where they proliferate and mature. The erythrocyte cytoplasm has very low [Ca2+] (<100 nM), which is very different from the extracellular environment encountered by most eukaryotic cells. The absence of extracellular Ca2+ is usually incompatible with normal cell functions and survival. In the present work, we have tested the possibility that Plasmodia overcome the limitation posed by the erythrocyte intracellular environment through the maintenance of a high [Ca2+] within the parasitophorous vacuole (PV), the compartment formed during invasion and within which the parasites grow and divide. Thus, Plasmodia were allowed to invade erythrocytes in the presence of Ca2+ indicator dyes. This allowed selective loading of the Ca2+ probes within the PV. The [Ca2+] within this compartment was found to be approximately 40 microM, i.e., high enough to be compatible with a normal loading of the Plasmodia intracellular Ca2+ stores, a prerequisite for the use of a Ca2+-based signaling mechanism. We also show that reduction of extracellular [Ca2+] results in a slow depletion of the [Ca2+] within the PV. A transient drop of [Ca2+] in the PV for a period as short as 2 h affects the maturation process of the parasites within the erythrocytes, with a major reduction 48 h later in the percentage of schizonts, the form that re-invades the red blood cells.

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Schematic model of Ca2+ compartmentation in Plasmodium-infected RBC. PVM, parasitophorous vacuolar membrane; ER, endoplasmic reticulum; N, nucleus.
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fig7: Schematic model of Ca2+ compartmentation in Plasmodium-infected RBC. PVM, parasitophorous vacuolar membrane; ER, endoplasmic reticulum; N, nucleus.

Mentions: The sequencing of the Plasmodium genome (Gardner et al., 2002) and several recent studies have identified in this parasite a number of signaling molecules related to those of vertebrate cells, including many proteins concerned with Ca2+ handling and signaling (Dyer and Day, 2000; Le Roch et al., 2000; Marchesini et al., 2000). The key question addressed here is how the parasite can use Ca2+-based signaling mechanisms while located within the RBC, where it might be expected to be exposed to a very low [Ca2+]. We have shown unambiguously that the PV provides a sufficiently high [Ca2+] to ensure the maintenance of the parasite Ca2+ stores (represented in Fig. 7) , and thus the sensitivity to agents, such as melatonin, that use Ca2+ as a second messenger to regulate the Plasmodia cell cycle (Hotta et al., 2000). In addition, a prolonged decrease of the [Ca2+] of the PV appears to impair the maturation of the parasites, and eventually is incompatible with the survival of the Plasmodia within the RBC.


Calcium signaling in a low calcium environment: how the intracellular malaria parasite solves the problem.

Gazarini ML, Thomas AP, Pozzan T, Garcia CR - J. Cell Biol. (2003)

Schematic model of Ca2+ compartmentation in Plasmodium-infected RBC. PVM, parasitophorous vacuolar membrane; ER, endoplasmic reticulum; N, nucleus.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172890&req=5

fig7: Schematic model of Ca2+ compartmentation in Plasmodium-infected RBC. PVM, parasitophorous vacuolar membrane; ER, endoplasmic reticulum; N, nucleus.
Mentions: The sequencing of the Plasmodium genome (Gardner et al., 2002) and several recent studies have identified in this parasite a number of signaling molecules related to those of vertebrate cells, including many proteins concerned with Ca2+ handling and signaling (Dyer and Day, 2000; Le Roch et al., 2000; Marchesini et al., 2000). The key question addressed here is how the parasite can use Ca2+-based signaling mechanisms while located within the RBC, where it might be expected to be exposed to a very low [Ca2+]. We have shown unambiguously that the PV provides a sufficiently high [Ca2+] to ensure the maintenance of the parasite Ca2+ stores (represented in Fig. 7) , and thus the sensitivity to agents, such as melatonin, that use Ca2+ as a second messenger to regulate the Plasmodia cell cycle (Hotta et al., 2000). In addition, a prolonged decrease of the [Ca2+] of the PV appears to impair the maturation of the parasites, and eventually is incompatible with the survival of the Plasmodia within the RBC.

Bottom Line: This allowed selective loading of the Ca2+ probes within the PV.The [Ca2+] within this compartment was found to be approximately 40 microM, i.e., high enough to be compatible with a normal loading of the Plasmodia intracellular Ca2+ stores, a prerequisite for the use of a Ca2+-based signaling mechanism.We also show that reduction of extracellular [Ca2+] results in a slow depletion of the [Ca2+] within the PV.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo 05508-900, Brazil.

ABSTRACT
Malaria parasites, Plasmodia, spend most of their asexual life cycle within red blood cells, where they proliferate and mature. The erythrocyte cytoplasm has very low [Ca2+] (<100 nM), which is very different from the extracellular environment encountered by most eukaryotic cells. The absence of extracellular Ca2+ is usually incompatible with normal cell functions and survival. In the present work, we have tested the possibility that Plasmodia overcome the limitation posed by the erythrocyte intracellular environment through the maintenance of a high [Ca2+] within the parasitophorous vacuole (PV), the compartment formed during invasion and within which the parasites grow and divide. Thus, Plasmodia were allowed to invade erythrocytes in the presence of Ca2+ indicator dyes. This allowed selective loading of the Ca2+ probes within the PV. The [Ca2+] within this compartment was found to be approximately 40 microM, i.e., high enough to be compatible with a normal loading of the Plasmodia intracellular Ca2+ stores, a prerequisite for the use of a Ca2+-based signaling mechanism. We also show that reduction of extracellular [Ca2+] results in a slow depletion of the [Ca2+] within the PV. A transient drop of [Ca2+] in the PV for a period as short as 2 h affects the maturation process of the parasites within the erythrocytes, with a major reduction 48 h later in the percentage of schizonts, the form that re-invades the red blood cells.

Show MeSH
Related in: MedlinePlus