Protein export in malaria parasites: many membranes to cross

Marti, Matthias; Spielmann, Tobias

doi:10.1016/j.mib.2013.04.010

Cited by 38 publications

(27 citation statements)

References 54 publications

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“…This sequence element is cleaved by endoplasmic reticulum-located proteases and the N terminus becomes acetylated (Ac-Xaa-Glu/Asp/Gln) (Chang et al, 2008;Boddey et al, 2009Boddey et al, , 2010Russo et al, 2010). The conserved spatial position of the PEXEL motif and its very rapid proteolytic modification are necessary for the export of effector proteins and seem to work as an internal signal for a specialized effector export pathway (Marti and Spielmann, 2013;Boddey et al, 2016). Recently, a similar motif (TEXEL) was found in effector proteins of Toxoplasma gondii and reported to play a crucial role in effector maturation and sorting during the infection process (Hammoudi et al, 2015;Coffey et al, 2015;Curt-Varesano et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

The RxLR Motif of the Host Targeting Effector AVR3a of Phytophthora infestans Is Cleaved before Secretion

et al. 2017

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Section: Introductionmentioning

confidence: 99%

The RxLR Motif of the Host Targeting Effector AVR3a of Phytophthora infestans Is Cleaved before Secretion

et al. 2017

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“…Indeed in Plasmodium, a substantial number of PEXELnegative exported proteins (PNEPs) have been already characterized (Heiber et al, 2013). In general, PNEPs do not contain the classical N-terminal SP either but the latter is somehow functionally compensated by the presence of a single internal hydrophobic stretch for targeting to the ER (Boddey and Cowman, 2013b;Marti and Spielmann, 2013). In Toxoplasma, the secreted protein GRA15 does not contain a canonical N-terminal SP (according to SignalP) but carries instead two transmembrane domains.…”

Section: Gra24 Discovery Uncovers a New Regulatory Path Distinct Frommentioning

confidence: 99%

“…Transport across the PVM of PEXEL/HT motif containing Plasmodium proteins is thought to involve a translocon, the PTEX complex (Plasmodium Translocon for Exported Proteins) inserted in the PVM (reviewed in (Boddey and Cowman, 2013b;Marti and Spielmann, 2013)). The PEXEL motif is not the element directly recognized by the so-called translocon and is instead a protease recognition site that is cleaved in the endoplasmic reticulum (ER) of the parasite before export (Boddey and Cowman, 2013b;Marti and Spielmann, 2013).…”

Section: Gra24 Discovery Uncovers a New Regulatory Path Distinct Frommentioning

confidence: 99%

“…The PEXEL motif is not the element directly recognized by the so-called translocon and is instead a protease recognition site that is cleaved in the endoplasmic reticulum (ER) of the parasite before export (Boddey and Cowman, 2013b;Marti and Spielmann, 2013). In the next step, PEXEL-containing proteins are matured by the Plasmepsin V protease, and the newly exposed N-terminal sequence is likely recognized by the translocation machinery (Boddey and Cowman, 2013b;Marti and Spielmann, 2013). Amino acids within the PEXEL motif after cleavage were shown to be important for export (Gruring et al, 2012;Boddey et al, 2013a;Tarr et al, 2013).…”

Section: Gra24 Discovery Uncovers a New Regulatory Path Distinct Frommentioning

confidence: 99%

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Toxoplasmaexports dense granule proteins beyond the vacuole to the host cell nucleus and rewires the host genome expression

2014

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SummaryToxoplasma gondii is the most widespread apicomplexan parasite and occupies a large spectrum of niches by infecting virtually any warmblooded animals. As an obligate intracellular parasite, Toxoplasma has evolved a repertoire of strategies to fine-tune the cellular environment in an optimal way to promote growth and persistence in host tissues hence increasing the chance to be transmitted to new hosts. Short and long-term intracellular survival is associated with Toxoplasma ability to both evade the host deleterious immune defences and to stimulate a beneficial immune balance by governing host cell gene expression. It is only recently that parasite proteins responsible for driving these transcriptional changes have been identified. While proteins contained in the apical secretory Rhoptry organelle have already been identified as bona fide secreted effectors that divert host signalling pathways, recent findings revealed that dense granule proteins should be added to the growing list of effectors as they reach the host cell cytoplasm and nucleus and target various host cell pathways in the course of cell infection. Herein, we emphasize on a novel subfamily of dense granule resident proteins, exemplified with the GRA16 and GRA24 members we recently discovered as both are exported beyond the vacuole-containing parasites and reach the host cell nucleus to reshape the host genome expression.

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“…Not only PEXEL motif-carrying proteins were found to be exported; there is a growing body of evidence for non-PEXEL-carrying proteins to be exported to the host cytosol, which includes proteins that do not even contain a recognizable N-terminal ER-targeting signal peptide (92,93,(98)(99)(100)(101). This group of proteins includes some wellcharacterized proteins known to be located to the Maurer's clefts, including Maurer's clefts resident proteins MAHRP1, SBP1, REX1, and REX2 (40,43,83,102,103), as well as the tether protein MAHRP2 (48).…”

Section: Proteins Reach Maurer's Clefts Via a Complex Transport Pathwaymentioning

confidence: 99%

Maurer's clefts, the enigma of Plasmodium falciparum

Mundwiler-Pachlatko

Beck

2013

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

104

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Plasmodium falciparum, the causative agent of malaria, completely remodels the infected human erythrocyte to acquire nutrients and to evade the immune system. For this process, the parasite exports more than 10% of all its proteins into the host cell cytosol, including the major virulence factor PfEMP1 (P. falciparum erythrocyte surface protein 1). This unusual protein trafficking system involves long-known parasitederived membranous structures in the host cell cytosol, called Maurer's clefts. However, the genesis, role, and function of Maurer's clefts remain elusive. Similarly unclear is how proteins are sorted and how they are transported to and from these structures. Recent years have seen a large increase of knowledge but, as yet, no functional model has been established. In this perspective we review the most important findings and conclude with potential possibilities to shed light into the enigma of Maurer's clefts. Understanding the mechanism and function of these structures, as well as their involvement in protein export in P. falciparum, might lead to innovative control strategies and might give us a handle with which to help to eliminate this deadly parasite.

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Protein export in malaria parasites: many membranes to cross

Cited by 38 publications

References 54 publications

The RxLR Motif of the Host Targeting Effector AVR3a of Phytophthora infestans Is Cleaved before Secretion

The RxLR Motif of the Host Targeting Effector AVR3a of Phytophthora infestans Is Cleaved before Secretion

Toxoplasmaexports dense granule proteins beyond the vacuole to the host cell nucleus and rewires the host genome expression

Maurer's clefts, the enigma of Plasmodium falciparum

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