The Exoneme Helps Malaria Parasites to Break out of Blood Cells

Janse, Chris J.; Waters, Andrew P.

doi:10.1016/j.cell.2007.11.026

Cited by 7 publications

(6 citation statements)

References 15 publications

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“…The subtilisin-like serine protease PfSUB1 is thought to have an essential function, since a gene deletion attempt was unsuccessful, which is in line with the observation that pharmacological inhibition of PfSUB1 activity blocks egress and ablates the invasive capacity of merozoites [48]. PfSUB1 localises to dense granule-like structures, termed exonemes, which are present at the apical end of the individual merozoite [51]. Prior to egress, PfSUB1 is discharged into the PV lumen, where it is believed to mediate proteolytic activation of a family of papain-like serine rich antigen proteases (SERAs), which have further roles in completing the egress cascade [48].…”

Section: Potential Molecular Mechanisms Regulated By Pfpkgmentioning

confidence: 73%

The role of cGMP signalling in regulating life cycle progression of Plasmodium

Hopp¹,

Bowyer²,

Baker³

2012

Microbes and Infection

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The 3′-5′-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is the main mediator of cGMP signalling in the malaria parasite. This article reviews the role of PKG in Plasmodium falciparum during gametogenesis and blood stage schizont rupture, as well as the role of the Plasmodium berghei orthologue in ookinete differentiation and motility, and liver stage schizont development. The current views on potential effector proteins downstream of PKG and the mechanisms that may regulate cyclic nucleotide levels are presented.

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Section: Potential Molecular Mechanisms Regulated By Pfpkgmentioning

confidence: 73%

The role of cGMP signalling in regulating life cycle progression of Plasmodium

Hopp¹,

Bowyer²,

Baker³

2012

Microbes and Infection

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“…Recently, PfPKG was reported to regulate the initiation of the proteolytic cascade prior to egress that involves the subtilisin-like serine protease 1 (PfSUB1) [13]. PfSUB1 is maximally expressed in late P. falciparum blood stage schizonts [14] and localises to dense granule-like structures, termed exonemes, that are present at the apical end of the individual merozoite [15]. Prior to egress, PfSUB1 is discharged into the parasitophorous vacuole, where it proteolytically cleaves the serine repeat antigens (PfSERAs) and components of the merozoite surface protein 1 (PfMSP1) complex [14], [16].…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal and Functional Characterisation of the Plasmodium falciparum cGMP-Dependent Protein Kinase

et al. 2012

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Signalling by 3′–5′-cyclic guanosine monophosphate (cGMP) exists in virtually all eukaryotes. In the apicomplexan parasite Plasmodium, the cGMP-dependent protein kinase (PKG) has previously been reported to play a critical role in four key stages of the life cycle. The Plasmodium falciparum isoform (PfPKG) is essential for the initiation of gametogenesis and for blood stage schizont rupture and work on the orthologue from the rodent malaria parasite P. berghei (PbPKG) has shown additional roles in ookinete differentiation and motility as well as liver stage schizont development. In the present study, PfPKG expression and subcellular location in asexual blood stages was investigated using transgenic epitope-tagged PfPKG-expressing P. falciparum parasites. In Western blotting experiments and immunofluorescence analysis (IFA), maximal PfPKG expression was detected at the late schizont stage. While IFA suggested a cytosolic location, a degree of overlap with markers of the endoplasmic reticulum (ER) was found and subcellular fractionation showed some association with the peripheral membrane fraction. This broad localisation is consistent with the notion that PfPKG, as with the mammalian orthologue, has numerous cellular substrates. This idea is further supported by the global protein phosphorylation pattern of schizonts which was substantially changed following PfPKG inhibition, suggesting a complex role for PfPKG during schizogony.

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“…Next step involves the high affinity attachment between the apical end of the merozoites and erythrocytes, resulting in the formation of a moving junction. Finally the merozoite invagination into the erythrocyte occurs via formation of a parasitophorous vacuole. − Merozoite invasion is orchestrated by proteins released from its apical secretory organelles  micronemes, rhoptries, and dense granules including exonemes . At the time of invasion, these proteins are released in a timely and spatially coordinated manner to facilitate parasite release, its invasion into the erythrocyte and formation of parasitophorous vacuole in which the parasite resides after invasion. − Studies in Toxoplasma have demonstrated that micronemes secrete their contents first, followed by secretion from rhoptries and dense granules…”

Section: Introductionmentioning

confidence: 99%

Proteome Analysis Reveals a Large Merozoite Surface Protein-1 Associated Complex on the Plasmodium falciparum Merozoite Surface

et al. 2010

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Plasmodium merozoite surface protein-1 (MSP-1) is an essential antigen for the merozoite invasion of erythrocytes. A key challenge to the development of an effective malaria vaccine that can block the erythrocyte invasion is to establish the molecular interaction(s) among the parasite surface proteins as well as with the host cell encoded receptors. In the present study, we applied molecular interactions and proteome approaches to identify PfMSP-1 associated complex on the merozoite surface. Proteomic analysis identified a major malaria surface protein, PfRhopH3 interacting with PfMSP-1(42). Pull-down experiments with merozoite lysate using anti-PfMSP-1 or anti-PfRhopH3 antibodies showed 16 bands that when identified by tandem mass spectrometry corresponded to11 parasite proteins: PfMSP-3, PfMSP-6, PfMSP-7, PfMSP-9, PfRhopH3, PfRhopH1, PfRAP-1, PfRAP-2, and two RAP domain containing proteins. This MSP-1 associated complex was specifically seen at schizont/merozoite stages but not the next ring stage. We could also identify many of these proteins in culture supernatant, suggesting the shedding of the complex. Interestingly, the PfRhopH3 protein also showed binding to the human erythrocyte and anti-PfRhopH3 antibodies blocked the erythrocyte invasion of the merozoites. These results have potential implications in the development of PfMSP-1 based blood stage malaria vaccine.

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The Exoneme Helps Malaria Parasites to Break out of Blood Cells

Cited by 7 publications

References 15 publications

The role of cGMP signalling in regulating life cycle progression of Plasmodium

The role of cGMP signalling in regulating life cycle progression of Plasmodium

Spatiotemporal and Functional Characterisation of the Plasmodium falciparum cGMP-Dependent Protein Kinase

Proteome Analysis Reveals a Large Merozoite Surface Protein-1 Associated Complex on the Plasmodium falciparum Merozoite Surface

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