An Unusual ERAD-Like Complex Is Targeted to the Apicoplast of<i>Plasmodium falciparum</i>

Spork, Simone; Hiss, Jan A.; Mandel, Katharina; Sommer, Maik S.; Kooij, Taco W. A.; Chu, Trang T. T.; Schneider, Gisbert; Maier, Uwe G.; Przyborski, Jude M.

doi:10.1128/ec.00083-09

Cited by 133 publications

(136 citation statements)

References 61 publications

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“…carry the transit peptide at the N terminus. This is an observation, which is seen not only in diatoms, but also in Apicomplexa (27) and might be a result of overexpression. However, all processing variants of the protein are glycosylated (Fig.…”

Section: Resultsmentioning

confidence: 70%

Evidence for glycoprotein transport into complex plastids

Peschke¹,

Moog

Klingl

et al. 2013

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

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Diatoms are microalgae that possess so-called "complex plastids," which evolved by secondary endosymbiosis and are surrounded by four membranes. Thus, in contrast to primary plastids, which are surrounded by only two membranes, nucleus-encoded proteins of complex plastids face additional barriers, i.e., during evolution, mechanisms had to evolve to transport preproteins across all four membranes. This study reveals that there exist glycoproteins not only in primary but also in complex plastids, making transport issues even more complicated, as most translocation machineries are not believed to be able to transport bulky proteins. We show that plastidal reporter proteins with artificial N-glycosylation sites are indeed glycosylated during transport into the complex plastid of the diatom Phaeodactylum tricornutum. Additionally, we identified five endogenous glycoproteins, which are transported into different compartments of the complex plastid. These proteins get N-glycosylated during transport across the outermost plastid membrane and thereafter are transported across the second, third, and fourth plastid membranes in the case of stromal proteins. The results of this study provide insights into the evolutionary pressure on translocation mechanisms and pose unique questions on the operating mode of well-known transport machineries like the translocons of the outer/inner chloroplast membranes (Toc/Tic).

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Section: Resultsmentioning

confidence: 70%

Evidence for glycoprotein transport into complex plastids

Peschke¹,

Moog

Klingl

et al. 2013

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

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“…Plasmodium possesses a conventional ERAD system. In addition, there is growing evidence of an ERAD-like pathway that is involved in protein translocation to the parasite-specific plastid, namely the apicoplast (11,51), the essentiality of which for the parasite's survival is clearly established (see Ref. 52 for a review).…”

Section: Discussionmentioning

confidence: 99%

“…The two ubiquitin fusion proteins PfUB S27a and PfUB L40 (PF14_0027 and PF13_0346, respectively) contain a ubiquitin moiety at their N-terminal side (10). More recently, one conserved ubiquitin domain was identified in PF08_0067 and is believed to be part of an endoplasmic reticulum-associated protein degradation (ERAD) 3 -like pathway (11). In addition to these four genes encoding ubiquitins, more than 100 proteins involved in the ubiquitylation system were identified in silico (10) (i.e.…”

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confidence: 99%

Unraveling the Ubiquitome of the Human Malaria Parasite

Ponts

Saraf

Chung

et al. 2011

Journal of Biological Chemistry

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Malaria is one of the deadliest infectious diseases worldwide. The most severe form is caused by the eukaryotic protozoan parasite Plasmodium falciparum. Recent studies have highlighted the importance of post-translational regulations for the parasite's progression throughout its life cycle, protein ubiquitylation being certainly one of the most abundant. The specificity of its components and the wide range of biological processes in which it is involved make the ubiquitylation pathway a promising source of suitable targets for anti-malarial drug development. Here, we combined immunofluorescent microscopy, biochemical assays, in silico prediction, and mass spectrometry analysis using the multidimensional protein identification technology, or MudPIT, to describe the P. falciparum ubiquitome. We found that ubiquitin conjugates are detected at every morphological stage of the parasite erythrocytic cycle. Furthermore, we detected that more than half of the parasite's proteome represents possible targets for ubiquitylation, especially proteins found to be present at the most replicative stage of the asexual cycle, the trophozoite stage. A large proportion of ubiquitin conjugates were also detected at the schizont stage, consistent with a cell activity slowdown to prepare for merozoite differentiation and invasion. Finally, for the first time in the human malaria parasite, our results strongly indicate the presence of heterologous mixed conjugations, SUMO/UB. This discovery suggests that sumoylated proteins may be regulated by ubiquitylation in P. falciparum. Altogether, our results present the first stepping stone toward a better understanding of ubiquitylation and its role(s) in the biology of the human malaria parasite.

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“…This process is supposed to be uncoupled from degradation. SELMA is conserved in all secondary evolved organisms with a red algal endosymbiont, for which genomic data are available (26,67,68). Proteins of the derlin family are still controversially discussed elements of the ERAD-specific translocon.…”

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confidence: 99%

Distribution of the SELMA Translocon in Secondary Plastids of Red Algal Origin and Predicted Uncoupling of Ubiquitin-Dependent Translocation from Degradation

et al. 2012

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cProtein import into complex plastids of red algal origin is a multistep process including translocons of different evolutionary origins. The symbiont-derived ERAD-like machinery (SELMA), shown to be of red algal origin, is proposed to be the transport system for preprotein import across the periplastidal membrane of heterokontophytes, haptophytes, cryptophytes, and apicomplexans. In contrast to the canonical endoplasmic reticulum-associated degradation (ERAD) system, SELMA translocation is suggested to be uncoupled from proteasomal degradation. We investigated the distribution of known and newly identified SELMA components in organisms with complex plastids of red algal origin by intensive data mining, thereby defining a set of core components present in all examined organisms. These include putative pore-forming components, a ubiquitylation machinery, as well as a Cdc48 complex. Furthermore, the set of known 20S proteasomal components in the periplastidal compartment (PPC) of diatoms was expanded. These newly identified putative SELMA components, as well as proteasomal subunits, were in vivo localized as PPC proteins in the diatom Phaeodactylum tricornutum. The presented data allow us to speculate about the specific features of SELMA translocation in contrast to the canonical ERAD system, especially the uncoupling of translocation from degradation.O rganelles such as plastids, including those of secondary origin, almost completely rely on protein import from the host cytosol (46, 65). The structure of complex plastids, surrounded by three or four membranes required, in contrast to primary plastids, the evolution of several additional protein transport mechanisms. Complex plastids arose through secondary endosymbiosis, a process which describes the engulfment of a former free-living eukaryotic alga into a eukaryotic host cell (32, 33). During evolution, the symbiont was subsequently reduced in terms of compartmentalization and genome size to an organelle strictly dependent on the host cell (16,32). Different types of secondary plastids exist in a very broad range of algae and protists, which can be distinguished based on their evolutionary origin (e.g., a red or green alga derived symbiont), as well as on the amount of cellular reduction inside the host cell. Our understanding of the evolution of organisms harboring a secondary plastid of red algal origin has changed in the last few years. According to the chromalveolate hypothesis, six major lineages were grouped together to be of monophyletic origin: cryptophytes, haptophytes, heterokontophytes, peridinincontaining dinoflagellates, apicomplexans, and the non-plastidcontaining ciliates, as well as several smaller lineages related to some chromalveolate members (15, 41). However, recent phylogenetic analyses have given rise to extended theories about the evolution of the lineages with a red algal endosymbiont, including serial endosymbiotic events with secondary, as well as tertiary, endosymbioses (21,22,26,27,56,61,71,75).It has been shown that the lineages wi...

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An Unusual ERAD-Like Complex Is Targeted to the Apicoplast ofPlasmodium falciparum

Cited by 133 publications

References 61 publications

Evidence for glycoprotein transport into complex plastids

Evidence for glycoprotein transport into complex plastids

Unraveling the Ubiquitome of the Human Malaria Parasite

Distribution of the SELMA Translocon in Secondary Plastids of Red Algal Origin and Predicted Uncoupling of Ubiquitin-Dependent Translocation from Degradation

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