Translocation of proteins across the multiple membranes of complex plastids

Dooren, Giel G. van; Schwartzbach, Steven D.; Osafune, Tetsuaki; McFadden, Geoffrey I.

doi:10.1016/s0167-4889(01)00154-9

Cited by 124 publications

(112 citation statements)

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“…It has been demonstrated in the heterokonts that the TPL functional domain localizes in the N-terminal portion (33). In euglenophytes and dinoflagellates, plastids are surrounded only by 3 membranes, and plastid preproteins are known to be transported from the ER to the plastids via Golgi bodies (8). The TPLs of these preproteins typically possess a remarkable hydrophobic region, which is known to act as a stop-transfer membrane anchor during the vesicular transportation via the Golgi bodies (14,15).…”

Section: Er-to-plastid Transport Signal In the Tplmentioning

confidence: 99%

“…In these endosymbiotic processes, numerous genes have transferred from the endosymbionts to the nuclear genomes of the host (6,7), and the proteins expressed from these genes need to be sent back into the plastids (i.e., the former endosymbionts) across multiple plastid membranes (8)(9)(10). To be targeted correctly into the plastids, the precursors of nuclear-encoded plastid proteins generally possess plastid-targeting presequences (11).…”

mentioning

confidence: 99%

“…However, the preproteins for diverse secondary plastids commonly have N-terminal bipartite plastid-targeting sequences, each of which consists of a signal peptide (SP) and a TP-like (TPL) sequence (11). The SP is known, in several groups with secondary plastids, to be responsible for the cotranslational transport of preproteins into the endoplasmic reticulum (ER), and the TPL is believed to be necessary for targeting the preproteins into the plastid stroma across multiple envelope membranes (8)(9)(10)(11).…”

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confidence: 99%

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Protein targeting into secondary plastids of chlorarachniophytes

Hirakawa

Nagamune²,

Ishida³

2009

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

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Most plastid proteins are encoded by the nuclear genome, and consequently, need to be transported into plastids across multiple envelope membranes. In diverse organisms possessing secondary plastids, nuclear-encoded plastid precursor proteins (preproteins) commonly have an N-terminal extension that consists of an endoplasmic reticulum (ER)-targeting signal peptide and a transit peptide-like sequence (TPL). This bipartite targeting peptide is believed to be necessary for targeting the preproteins into the secondary plastids. Here, we newly demonstrate the function of the bipartite targeting peptides of an algal group, chlorarachniophytes, and characterize the functional domains of the TPL in the precursor of a plastid protein, ATP synthase delta subunit (AtpD), using a GFP as a reporter molecule. We show that the C-terminal portion of the TPL is important for targeting the AtpD preprotein from the ER into the chlorarachniophyte plastids, and several positively charged amino acids in the TPL are also necessary for transporting the preprotein across the 2 innermost plastid membranes. Compared with other groups with secondary plastids, the TPL functional domains of the chlorarachniophytes are unique, which might be caused by independent acquisition of their plastids.ATP synthase delta subunit ͉ secondary endosymbiosis ͉ transit peptides ͉ bipartite targeting peptide ͉ periplastidal compartment

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Section: Er-to-plastid Transport Signal In the Tplmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Protein targeting into secondary plastids of chlorarachniophytes

Hirakawa

Nagamune²,

Ishida³

2009

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

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“…Proteins targeted to the plastids of several other phyla require a bipartite leader similar to that of P. falciparum (see review in Ref. 46), and evidence suggests that the apicoplast shares a common secondary endosymbiotic origin with many of these (47,48). The cleavage sites of a few heterokont (brown algal and diatom) and cryptomonad proteins have been identified or predicted (49 -51), with many containing a methionine residue in the -1 position (50,51).…”

Section: Figmentioning

confidence: 99%

Processing of an Apicoplast Leader Sequence inPlasmodium falciparum and the Identification of a Putative Leader Cleavage Enzyme

Dooren¹,

D’Ombrain

et al. 2002

Journal of Biological Chemistry

164

167

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The plastid (apicoplast) of the malaria-causing parasite Plasmodium falciparum was derived via a secondary endosymbiotic process. As in other secondary endosymbionts, numerous genes for apicoplast proteins are located in the nucleus, and the encoded proteins are targeted to the organelle courtesy of a bipartite N-terminal extension. The first part of this leader sequence is a signal peptide that targets proteins to the secretory pathway. The second, so-called transit peptide region is required to direct proteins from the secretory pathway across the multiple membranes surrounding the apicoplast. In this paper we perform a pulse-chase experiment and N-terminal sequencing to show that the transit peptide of an apicoplast-targeted protein is cleaved, presumably upon import of the protein into the apicoplast. We identify a gene whose product likely performs this cleavage reaction, namely a stromal-processing peptidase (SPP) homologue. In plants SPP cleaves the transit peptides of plastid-targeted proteins. The P. falciparum SPP homologue contains a bipartite N-terminal apicoplast-targeting leader. Interestingly, it shares this leader sequence with a ⌬-aminolevulinic acid dehydratase homologue via an alternative splicing event.Plasmodium spp., the causative agents of malaria, belong to a family of intracellular parasites called the Apicomplexa. Plasmodium infects approximately 300 million people annually, causing over 1 million deaths, the great majority of which are caused by one species, Plasmodium falciparum (1). P. falciparum infects both humans and mosquitoes during its life cycle, with the pathogenic part of this cycle occurring predominantly in the erythrocytes of humans. The discovery of a non-photosynthetic plastid (the apicoplast) in the Apicomplexa has opened up a new area of anti-malarial drug targets (2, 3). However, the rational development of drugs targeting the apicoplast requires knowledge of apicoplast function. Preliminary studies indicate that the apicoplast is a site of fatty acid and isoprenoid biosynthesis (4 -6), and drugs targeting these pathways have been shown to kill P. falciparum (4, 6, 7).Like plant plastids, the apicoplast contains a reduced bacterial-like genome (8), from which a small number of proteins are expressed. The great majority of apicoplast proteins, as in plant plastids, are encoded in the nucleus and must be post-translationally targeted to the plastid. In plants, nuclear-encoded plastid proteins require a cleavable, N-terminal sequence called the transit peptide, which directs these proteins across the two membranes surrounding plant plastids (for reviews, see Refs. 9 and 10). Once in the plastid stroma, this transit peptide is cleaved by a stromal-processing peptidase (SPP 1 ; Refs. 11 and 12). Apicoplasts, however, are bound by four membranes (Ref. 2, but see Ref. 13), and proteins targeted to this organelle have been shown to require a bipartite N-terminal leader sequence (5,14,15). By fusing these N-terminal leader sequences to green fluorescent reporter protein (GFP)...

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“…The remaining proteins are thought to be packaged into vesicles that bud from the outer membrane of the apicoplast for transport to further destinations in the secretory pathway, culminating in secretion into the parasitophorous vacuole. Toc and Tic complexes are believed to mediate protein import across the two innermost membranes of the apicoplast in an ATP-dependent fashion (25). Following protein import, the transit peptide is cleaved by a stromal processing peptidase homologue in the apicoplast (26), so that following its targeting to the apicoplast, the processed NEAT protein is of lower molecular mass than the preprocessed form.…”

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confidence: 99%

15-Deoxyspergualin Primarily Targets the Trafficking of Apicoplast Proteins in Plasmodium falciparum

Ramya

Karmodiya

Surolia

et al. 2007

Journal of Biological Chemistry

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15-Deoxyspergualin, an immunosuppressant with tumoricidal and antimalarial properties, has been implicated in the inhibition of a diverse array of cellular processes including polyamine synthesis and protein synthesis. Endeavoring to identify the mechanism of antimalarial action of this molecule, we examined its effect on Plasmodium falciparum protein synthesis, polyamine biosynthesis, and transport. 15-Deoxyspergualin stalled protein synthesis in P. falciparum through Hsp70 sequestration and subsequent phosphorylation of the eukaryotic initiation factor eIF2␣. However, protein synthesis inhibition as well as polyamine depletion were invoked only by high micromolar concentrations of 15-deoxyspergualin, in contrast to the submicromolar concentrations sufficient to inhibit parasite growth. Further investigations demonstrated that 15-deoxyspergualin in the malaria parasite primarily targets the hitherto underexplored process of trafficking of nucleus-encoded proteins to the apicoplast. Our finding that 15-deoxyspergualin kills the malaria parasite by interfering with targeting of nucleus-encoded proteins to the apicoplast not only exposes a chink in the armor of the malaria parasite, but also reveals new realms in our endeavors to study this intriguing biological process. 15-Deoxyspergualin (DSG)4 ( Fig. 1), an analog of spergualin isolated from the culture broth of Bacillus laterosporus, inhibits the growth of the malaria parasite, Plasmodium, in vitro and in vivo, presumably by depleting its polyamine reserves (1, 2). However, other known inhibitors of polyamine biosynthesis, methylglyoxal-bis-(guanylhydrazone) analog (MGBCP), irinotecan hydrochloride (CPT11), and ␣-difluoromethyl ornithine (DFMO) are known to be incapable of suppressing malaria in infected mice (2). This led us to question the speculated mechanism of antimalarial action of DSG.Despite the uncertainty in the actual mechanism of action of DSG, DSG is known to bind cellular chaperones, Hsp70 and Hsp90, potently, via their regulatory C-terminal motif EEVD (3, 4). DSG does not inhibit their chaperone activity (3-5). However, it selectively enhances the ATPase activity of heat shock proteins that have the C-terminal EEVD motif, and this could be the basis of a specific modulation of the function of proteins that bind the EEVD motif of heat shock proteins (5).One of the cellular milieus in which heat shock proteins are speculated to be involved is translational regulation. Translation of an mRNA requires the formation of a ternary complex of the methionyl-tRNA, the mRNA and the 40 S subunit of the ribosome, a feat achieved through the intervention of the GTPbound form of the initiation factor eIF2 (6). Phosphorylation of eIF2␣ at Ser 51 blocks protein synthesis by preventing eIF2 recycling and depleting the cell of its pool of eIF2-GTP required for translation initiation (7). Several conditions of cellular stress trigger the phosphorylation of eIF2␣ via the activation of four different eIF2␣ kinases: PERK (PKR-like endoplasmic reticulum-associated kina...

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Translocation of proteins across the multiple membranes of complex plastids

Cited by 124 publications

References 110 publications

Protein targeting into secondary plastids of chlorarachniophytes

Protein targeting into secondary plastids of chlorarachniophytes

Processing of an Apicoplast Leader Sequence inPlasmodium falciparum and the Identification of a Putative Leader Cleavage Enzyme

15-Deoxyspergualin Primarily Targets the Trafficking of Apicoplast Proteins in Plasmodium falciparum

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