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International Journal of Zoology and Animal Biology Research Article 10 min read

Cell Membrane Compartmentalization and Membrane Dynamics during Plasmodium Infection

Moumaris M*
* Corresponding author
ISSN: 2639-216X  10.23880/izab-16000637  Received: December 09, 2024  Published: December 18, 2024
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Keywords
Red Blood Cells Plasmodium Membrane Parasitophorous Vacuole Maurer’s Clefts Immunity
Abstract

Plasmodium undergoes a sophisticated invasion process to enter red blood cells (RBCs), a critical step in its life cycle. The invasion process is intricately regulated and involves a series of well-coordinated events. Membrane compartmentalization and dynamics play a central role in this process.

Abbreviations

CD47: Cluter of Differentiation; CR1: Complement Receptor Type 1; EBAs: Erythrocyte Binding Antigens; NPPs: New Permeability Pathways; PfEMP1: Plasmodium Falciparum Erythrocyte Membrane Protein 1; PV: Parasitophorous Vacuole; PVM: Parasitophorous Vacuole Membrane; RBCs: Red Blood Cells; RONs: Rhoptry Neck Proteins.

Plasmodium undergoes a sophisticated invasion process to enter red blood cells (RBCs), a critical step in its life cycle. The invasion process is intricately regulated and involves a series of well-coordinated events. Membrane compartmentalization and dynamics play a central role in this process. The parasite actively reorganizes its membranes and manipulates those of the host cell to facilitate its entry. Once inside, it resides within a parasitophorous vacuole, a membrane-bound compartment that shields it from the host’s immune defenses while allowing it to exploit host resources. Understanding molecular and cellular mechanisms underlying these membrane interactions provides valuable insights into potential therapeutic targets.

Figure 1
Click to enlarge
Figure 1

Membrane compartmentalization organizes the plasma membrane into distinct domains with specialized functions. Plasmodium infection takes advantage of this compartmentalization through various mechanisms. Lipids rafts, rich in cholesterol and sphingolipids, allow the parasite’s entry into host cells. These domains serve as platforms for receptor clustering, facilitating the interaction between the parasite and the host cell membrane. After invasion, Plasmodium resides within a parasitophorous vacuole (PV) derived from the host cell membrane. This compartment acts as a protective niche, separating the parasite from the host cytoplasm while allowing nutrient acquisition and waste disposal. The parasite induces compartmentalization within the host cell, forming structures such as Maurer’s clefts. These are membrane-bound compartments essential for protein trafficking and erythrocyte remodeling (Figure 1) [1, 2, 3].

Membrane dynamics encompass the processes of deformation, fusion, and trafficking within the cell membrane. The Plasmodium parasite exploits these mechanisms to support its lifecycle. A key stage is the invasion of erythrocytes by Plasmodium merozoites, a highly coordinated and complex process that induces transient deformations in the host cell membrane. The invasion begins with the merozoite reversibly attaching to the erythrocyte surface by binding to specific receptors, such as glycophorins and complement receptors. It is followed by an irreversible reorientation of the merozoite, aligning its apical pole with the erythrocyte membrane. A tight junction forms a specialized protein complex that establishes close contact between the merozoite and the host cell. This junction acts as a seal, guiding the invagination of the erythrocyte membrane to engulf the parasite, ultimately leading to the formation of the parasitophorous vacuole (PV). The PV is a specialized compartment that protects and nourishes the parasite within the host cell. During the formation of the PV, the parasite deploys proteins such as Rhoptry Neck Proteins (RONs) and Erythrocyte Binding Antigens (EBAs) to mediate membrane fusion events, ensuring a seamless entry into the host cell. These interactions are crucial for the successful invasion and survival of the parasite. The parasitophorous vacuolar membrane is a hybrid structure derived from the parasite and the erythrocyte, enabling the parasite to acquire nutrients and evade immune detection. During the invasion, the parasite sheds its surface coat. It releases contents from secretory organelles, each serving distinct functions. Micronemes facilitate adhesion and junction formation, rhoptries modify the host cell, and dense granules maintain the vacuole. This process showcases the parasite’s sophisticated adaptations for survival and growth within its host (Figure 2) [4, 5, 6].

Figure 2: Erythrocyte invasion by Plasmodium merozoite. A- Merozoite attachment. B- Merozoite reorientation and junction formation. C- Parasitophorous vacuole formation and invasion. D- Pinching off the junction and shedding of surface coat. E- Ring stage.
Click to enlarge
Figure 2: Erythrocyte invasion by Plasmodium merozoite. A- Merozoite attachment. B- Merozoite reorientation and junction formation. C- Parasitophorous vacuole formation and invasion. D- Pinching off the junction and shedding of surface coat. E- Ring stage.

Once inside an erythrocyte, Plasmodium reprograms the host cell to suit its survival needs. The parasite sends proteins across the parasitophorous vacuole membrane (PVM) into the host’s cytoplasm and membrane, triggering significant changes. These modifications affect the erythrocyte’s stiffness, permeability, and surface protein makeup. By creating New Permeability Pathways (NPPs) facilitated by parasite- formed channels and altered host transporters, the infected cell becomes more accessible to nutrients. Additionally, Plasmodium reshapes the erythrocyte’s cytoskeleton and lipid composition, increasing its flexibility-a vital adaptation that helps the parasite navigate narrow microcapillaries and evade splenic filtration [7].

Plasmodium parasites remodel red blood cells (RBCs) to survive and evade the host immune system. They form surface knobs packed with cytoadhesion proteins like PfEMP1 (Plasmodium falciparum Erythrocyte Membrane Protein 1), enabling infected RBCs to adhere to endothelial cells and avoid spleen clearance. Inside RBCs, the parasites reside in parasitophorous vacuoles, which contain tubo- vesicular networks and detergent-resistant membranes rich in lipids, supporting parasite growth and nutrient acquisition. The Maurer’s clefts direct parasite proteins like PfEMP1 to the RBC surface, ensuring functional knob formation and cytoadherence, which can lead to severe complications such as cerebral and placental malaria. Infected RBCs also exhibit increased metabolic activity, enhancing nutrient uptake and waste removal via modified membrane channels. While aiding parasite survival, these adaptations offer potential targets for therapeutic interventions and vaccine development. The ability of Plasmodium to manipulate membrane dynamics is essential to evade immune detection. In Plasmodium falciparum infections, the surface of infected red blood cells develops specialized protrusions known as knobs. These structures anchor cytoadherence proteins like PfEMP1, enabling the infected cells to adhere to microvascular walls and avoid clearance by the spleen. Additionally, the parasite alters or removes specific host membrane proteins, such as CD47 and CR1, to further reduce the likelihood of immune recognition (Figure 3) [8, 9].

Figure 3: Plasmodium-Infected Red Blood Cells. 1-Nucleus. 2- Endoplasmic reticulum. 3- Golgi apparatus. 4- Mitochondria. 5- Apicoplaste. 6- Digestive vacuole. 7- Parasite cytoplasm. 8- Parasitophorous Vacuole. 9- Tubo- vesicular Networks. 10- RBC cytoplasm. 11- Maurer’s clefts.
Click to enlarge
Figure 3: Plasmodium-Infected Red Blood Cells. 1-Nucleus. 2- Endoplasmic reticulum. 3- Golgi apparatus. 4- Mitochondria. 5- Apicoplaste. 6- Digestive vacuole. 7- Parasite cytoplasm. 8- Parasitophorous Vacuole. 9- Tubo- vesicular Networks. 10- RBC cytoplasm. 11- Maurer’s clefts.

A deeper understanding of membrane compartmentalization and dynamics during Plasmodium infection reveals promising therapeutic opportunities. Interfering with lipid rafts or receptor-ligand interactions could block merozoite entry while disrupting the export of parasite proteins, which could hinder erythrocyte remodeling and compromise parasite survival. Targeting membrane permeability, modulating New Permeability Pathways (NPPs), or inhibiting ion channels could deprive the parasite of essential nutrients. These processes are central to Plasmodium’s capacity to invade and thrive within host cells. The complex interaction between parasite and host membranes drives malaria pathogenesis and highlights critical vulnerabilities for intervention [10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39].

Acknowledgments

The author acknowledges Mrs. Norri Zahra and Mr. Regragui Moumaris. The author thinks Prof. Nisen Abuaf (Sorbonne University and AP-HP). The author thinks Tech. Said Youssouf Chanfi (Sorbonne University). The author thinks Ing. Jean-Michel Bretagne (AP-HP). The author thinks Clr. Marie-Hélène Maës and Clr. Monique Abi (Research and Development Company).

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@article{moumaris2024,
  title   = {Cell Membrane Compartmentalization and Membrane Dynamics
during Plasmodium Infection},
  author  = {Moumaris M},
  journal = {International Journal of Zoology and Animal Biology},
  year    = {2024},
  volume  = {7},
  number  = {6},
  doi     = {10.23880/izab-16000637}
}
Moumaris M (2024). Cell Membrane Compartmentalization and Membrane Dynamics
during Plasmodium Infection. International Journal of Zoology and Animal Biology, 7(6). https://doi.org/10.23880/izab-16000637
TY  - JOUR
TI  - Cell Membrane Compartmentalization and Membrane Dynamics
during Plasmodium Infection
AU  - Moumaris M
JO  - International Journal of Zoology and Animal Biology
PY  - 2024
VL  - 7
IS  - 6
DO  - 10.23880/izab-16000637
ER  -