Endocytosis in Plasmodium and Toxoplasma Parasites

Spielmann, Tobias; Gras, Simon; Sabitzki, Ricarda; Meissner, Markus

doi:10.1016/j.pt.2020.03.010

Cited by 62 publications

(74 citation statements)

References 85 publications

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“…The content of cytostomes has been assumed to be subsequently transported to the parasite's digestive vacuole (DV); however, it is important to note that this has yet to be experimentally shown; consequently, the mechanism(s) by which hemoglobin and the host cell cytosol are delivered from endocytic structures to the DVs is yet to be resolved. We refer readers to a review by Spielmann et al (2020) for proposed endocytic routes to the DV, which involve either the entire cytostome or only a portion pinching off and the subsequent transport to the DV, with potential involvement of intermediatory compartments. Digestion of hemoglobin occurs en route and within the DV (Abu Bakar et al, 2010), with the globin chains first cleaved from hemoglobin by aspartic proteases and cysteine endoproteases, and the liberated polypeptides then further digested by metalloproteases and series of aminopeptidases into oligopeptides and dipeptides to provide a source of amino acids for the parasite (Goldberg, 2005).…”

Section: Ingestion Of Host Hemoglobin Via Formation Of the Cytostomementioning

confidence: 99%

“…The molecular constituents that govern the uptake of the host cytosol by P. falciparum are also not resolved, largely because findings have either been conflicting or direct functional data have been lacking. We refer readers to two reviews that summarize the large body of work that has been undertaken to tease out potential molecular players in endocytosis of the host cell cytosol, with candidates including adapter protein-2 (AP-2), phosphatidylinositol-3-kinase, coronin, actin, dynamin, epidermal growth factor receptor substrate-15 (Eps15) homology domain (EHD) protein, soluble N-ethylmaleimide sensitive factor attachment protein (SNAP) receptor proteins (SNAREs), and Rab proteins (Spielmann et al, 2020;Xie et al, 2020). More recently, two studies from the Spielmann laboratory using genetic and proximity ligation approaches have shed further light on this process, revealing that components of a non-canonical endocytic apparatus are involved.…”

Section: Ingestion Of Host Hemoglobin Via Formation Of the Cytostomementioning

confidence: 99%

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How Malaria Parasites Acquire Nutrients From Their Host

Counihan

Modak

Koning-Ward

2021

Front. Cell Dev. Biol.

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Plasmodium parasites responsible for the disease malaria reside within erythrocytes. Inside this niche host cell, parasites internalize and digest host hemoglobin to source amino acids required for protein production. However, hemoglobin does not contain isoleucine, an amino acid essential for Plasmodium growth, and the parasite cannot synthesize it de novo. The parasite is also more metabolically active than its host cell, and the rate at which some nutrients are consumed exceeds the rate at which they can be taken up by erythrocyte transporters. To overcome these constraints, Plasmodium parasites increase the permeability of the erythrocyte membrane to isoleucine and other low-molecular-weight solutes it requires for growth by forming new permeation pathways (NPPs). In addition to the erythrocyte membrane, host nutrients also need to cross the encasing parasitophorous vacuole membrane (PVM) and the parasite plasma membrane to access the parasite. This review outlines recent advances that have been made in identifying the molecular constituents of the NPPs, the PVM nutrient channel, and the endocytic apparatus that transports host hemoglobin and identifies key knowledge gaps that remain. Importantly, blocking the ability of Plasmodium to source essential nutrients is lethal to the parasite, and thus, components of these key pathways represent potential antimalaria drug targets.

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Section: Ingestion Of Host Hemoglobin Via Formation Of the Cytostomementioning

confidence: 99%

Section: Ingestion Of Host Hemoglobin Via Formation Of the Cytostomementioning

confidence: 99%

How Malaria Parasites Acquire Nutrients From Their Host

Counihan

Modak

Koning-Ward

2021

Front. Cell Dev. Biol.

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“…and macromolecules (GFP and mCherry) from the host cytoplasm (9)(10)(11)(12). It has been proposed that tachyzoites ingest host cytoplasmic proteins via endocytosis at the micropore (13,14). Micropores have also been observed in bradyzoite cysts (13).…”

Section: Introductionmentioning

confidence: 99%

Acquisition of Host Cytosolic Protein byToxoplasma gondiiBradyzoites

Kannan

Thaprawat

Schultz

et al. 2020

Preprint

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Toxoplasma gondii is a protozoan parasite that persists in the central nervous system as intracellular chronic stage bradyzoites that are encapsulated by a thick cyst wall. While the cyst wall separates bradyzoites from the host cytosol, it has been posited that small solutes can traverse the cyst wall to sustain bradyzoites. Recently it was found that host cytosolic macromolecules can cross the parasitophorous vacuole and are ingested and digested by actively replicating acute stage tachyzoites. However, the extent to which bradyzoites have an active ingestion pathway remained unknown. To interrogate this, we modified previously published protocols that look at tachyzoite acquisition and digestion of host proteins by measuring parasite accumulation of a host-expressed reporter protein after impairment of an endolysosomal protease (Cathepsin Protease L, CPL). Using two cystogenic parasite strains (ME49 and Pru), we demonstrate that T. gondii bradyzoites can ingest host-derived cytosolic mCherry. Bradyzoites acquire host mCherry within 4 hours of invasion and post-cyst wall formation. This study provides direct evidence that host macromolecules can be internalized by T. gondii bradyzoites across the cyst wall in infected cells.

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“…The function of the Kelch13 compartment and cytostome-like structures in late schizont and merozoites remains to be elucidated. It could either represent a repurposing of these endocytosis-linked structures (Spielmann et al, 2020) for host cell invasion and the establishment of the parasite in a new host cell or serve an endocytosis-related function in schizonts, as it has been recently shown that schizonts still appear to endocytose host cell hemoglobin (Bisio et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Identification of novel inner membrane complex and apical annuli proteins of the malaria parasitePlasmodium falciparum

Wichers

Wunderlich

Heincke

et al. 2021

Preprint

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The inner membrane complex (IMC) is a defining feature of apicomplexan parasites, which confers stability and shape to the cell, functions as a scaffolding compartment during the formation of daughter cells and plays an important role in motility and invasion during different life cycle stages of these single celled organisms. To explore the IMC proteome of the malaria parasite Plasmodium falciparum we applied a proximity-dependent biotin identification (BioID)-based proteomics approach, using the established IMC marker protein Photosensitized INA-Labelled protein 1 (PhIL1) as bait in asexual blood-stage parasites. Subsequent mass spectrometry-based peptide identification revealed enrichment of twelve known IMC proteins and several uncharacterized candidate proteins. We validated nine of these previously uncharacterized proteins by endogenous GFP-tagging. Six of these represent new IMC proteins, while three proteins have a distinct apical localization that most likely represent structures described as apical annuli in Toxoplasma gondii. Additionally, various Kelch13 interacting candidates were identified, suggesting an association of the Kelch13 compartment and the IMC in schizont and merozoite stages. This work extends the number of validated IMC proteins in the malaria parasite and reveals for the first time the existence of apical annuli proteins in P. falciparum. Additionally, it provides evidence for a spatial association between the Kelch13 compartment and the IMC in late blood-stage parasites.

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Endocytosis in Plasmodium and Toxoplasma Parasites

Cited by 62 publications

References 85 publications

How Malaria Parasites Acquire Nutrients From Their Host

How Malaria Parasites Acquire Nutrients From Their Host

Acquisition of Host Cytosolic Protein byToxoplasma gondiiBradyzoites

Identification of novel inner membrane complex and apical annuli proteins of the malaria parasitePlasmodium falciparum

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