Mechanisms of Tail-Anchored Membrane Protein Targeting and Insertion

Chio, Un Seng; Cho, Hyunjun; Shan, Shu‐ou

doi:10.1146/annurev-cellbio-100616-060839

Cited by 103 publications

(113 citation statements)

References 99 publications

(213 reference statements)

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“…The TMS and its flanking residues of TA proteins, which are found solely in the MOM, are less hydrophobic and have a reduced helical content compared to those of ER TA proteins (a signal that is recognized by the guided entry of TA proteins [GET] pathway). Furthermore, the C‐terminal element (CTE) of such MOM TA protein is less charged than that in tail‐anchors of peroxisome proteins (a signal which is recognized by Pex19) . To prevent the TA proteins from aggregation, various cytosolic factors are ensuring their proper folding and delivery to the ER or peroxisomes …”

Section: Introductionmentioning

confidence: 99%

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Pex19 is involved in importing dually targeted tail‐anchored proteins to both mitochondria and peroxisomes

Cichocki

Krumpe

Vitali

et al. 2018

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Tail-anchored (TA) proteins are embedded into their corresponding membrane via a single transmembrane segment at their C-terminus whereas the majority of the protein is facing the cytosol. So far, cellular factors that mediate the integration of such proteins into the mitochondrial outer membrane were not found. Using budding yeast as a model system, we identified the cytosolic Hsp70 chaperone Ssa1 and the peroxisome import factor Pex19 as import mediators for a subset of mitochondrial TA proteins. Accordingly, deletion of PEX19 results in: (1) growth defect under respiration conditions, (2) alteration in mitochondrial morphology, (3) reduced steady-state levels of the mitochondrial TA proteins Fis1 and Gem1, and (4) hampered in organello import of the TA proteins Fis1 and Gem1. Furthermore, recombinant Pex19 can bind directly the TA proteins Fis1 and Gem1. Collectively, this work identified the first factors that are involved in the biogenesis of mitochondrial TA proteins and uncovered an unexpected function of Pex19.

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Section: Introductionmentioning

confidence: 99%

“…Furthermore, the C‐terminal element (CTE) of such MOM TA protein is less charged than that in tail‐anchors of peroxisome proteins (a signal which is recognized by Pex19) . To prevent the TA proteins from aggregation, various cytosolic factors are ensuring their proper folding and delivery to the ER or peroxisomes …”

Section: Introductionmentioning

confidence: 99%

Pex19 is involved in importing dually targeted tail‐anchored proteins to both mitochondria and peroxisomes

Cichocki

Krumpe

Vitali

et al. 2018

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“…For example, human Fis1 50,51 , yeast Fis1p 33 , and human Mff can be localized to both organelles 52 . The parameters that allow TAs to discriminate between peroxisomes, mitochondria, and other organelles are not understood, but may be related to the hydrophobicity of the membrane associated domain, along with the number and specific location of charges within the TA 53,54 . When considering the recent development of a classifier for peroxisome-directed mammalian TAs 54 , the GRAVY hydrophobicity score (1.7) 55 of the YgiM transmembrane domain, denoting more limited hydrophobicity, together with the net charge (+4.1) of the proposed lumenal tail at neutral pH (Protein Calculator v3.4, http://protcalc.sourceforge.net/) do, in fact, predict peroxisomal localization of the YgiM(TA).…”

Section: What Features Of Ygim(ta) Allow Targeting To Peroxisomes?mentioning

confidence: 99%

A bacteria-derived tail anchor localizes to peroxisomes in yeast and mammalian cells

Lutfullahoğlu-Bal

Seferoglu

Keskin

et al. 2018

Preprint

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This is a version of the manuscript prepared prior to incorporation of peer-reviewer comments. 2 ABSTRACTProkaryotes can provide new genetic information to eukaryotes by horizontal gene transfer (HGT), and such transfers are likely to have been particularly consequential at the dawn of eukaryogenesis. Since eukaryotes are highly compartmentalized, it is worthwhile to consider the mechanisms by which newly transferred proteins might reach diverse organellar destinations. Toward this goal, we have focused our attention upon the behavior of bacteria-derived tail anchors (TAs) expressed in the eukaryote Saccharomyces cerevisiae. In this study, we report that a predicted membrane-associated domain of the Escherichia coli YgiM protein is specifically trafficked to peroxisomes in budding yeast, can be found at a pre-peroxisomal compartment (PPC) upon disruption of peroxisomal biogenesis, and can functionally replace an endogenous peroxisome-directed TA. Furthermore, the YgiM(TA) can also localize to peroxisomes in mammalian cells. Since the YgiM(TA) plays no endogenous role in peroxisomal function or assembly, this domain is likely to serve as an excellent tool toward illumination of the mechanisms by which TAs can travel to peroxisomes. Moreover, our findings emphasize the ease with which bacteria-derived sequences might target to organelles in eukaryotic cells following HGT, and we discuss the importance of flexible recognition of organelle targeting information during and after eukaryogenesis.

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“…Consequently, all TA proteins are imported in membranes posttranslationally (Chio et al ., ; Costello et al ., ; ). In addition to mitochondria, TA proteins are components of other membrane‐bound organelles, such as the endoplasmic reticulum (ER), peroxisomes, and in plants, the outer membrane of plastids (Kriechbaumer et al ., ; Chio et al ., ; Costello et al ., ; ). Altogether, TA proteins represent 3–5% of the eukaryotic membrane proteome (Hegde and Keenan, ).…”

Section: Introductionmentioning

confidence: 98%

“…There are multiple pathways that assist in the posttranslational targeting of TA proteins to the ER. They are based on the interaction of TA proteins with (i) the signal recognition particle (SRP‐assisted insertion), (ii) the Hsc70/Hsp40 system of chaperones, (iii) targeting and insertion via the Guided Entry of TA protein (GET) pathway (Abell et al ., ; ; Schuldiner et al ., ; Rabu et al ., ; Brkljacic et al ., ; Colombo and Fasana, ; Chio et al ., ; Costello et al ., ; ) and (iv) the recently discovered SRP‐independent pathway (SND) that can partially substitute for the SRP and GET pathways (Aviram et al ., ; Casson et al ., ). The characteristic feature of the yeast ER proteins is a higher hydrophobicity of the TMD in comparison to the mitochondrial TA proteins, although this feature is not clearly different in human cells (Costello et al ., ; ).…”

Section: Introductionmentioning

confidence: 98%

Targeting of tail‐anchored proteins to Trichomonas vaginalis hydrogenosomes

Rada

Makki

Žárský

et al. 2019

Molecular Microbiology

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Summary Tail‐anchored (TA) proteins are membrane proteins that are found in all domains of life. They consist of an N‐terminal domain that performs various functions and a single transmembrane domain (TMD) near the C‐terminus. In eukaryotes, TA proteins are targeted to the membranes of mitochondria, the endoplasmic reticulum (ER), peroxisomes and in plants, chloroplasts. The targeting of these proteins to their specific destinations correlates with the properties of the C‐terminal domain, mainly the TMD hydrophobicity and the net charge of the flanking regions. Trichomonas vaginalis is a human parasite that has adapted to oxygen‐poor environment. This adaptation is reflected by the presence of highly modified mitochondria (hydrogenosomes) and the absence of peroxisomes. The proteome of hydrogenosomes is considerably reduced; however, our bioinformatic analysis predicted 120 putative hydrogenosomal TA proteins. Seven proteins were selected to prove their localization. The elimination of the net positive charge in the C‐tail of the hydrogenosomal TA4 protein resulted in its dual localization to hydrogenosomes and the ER, causing changes in ER morphology. Domain mutation and swap experiments with hydrogenosomal (TA4) and ER (TAPDI) proteins indicated that the general principles for specific targeting are conserved across eukaryotic lineages, including T. vaginalis; however, there are also significant lineage‐specific differences.

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Mechanisms of Tail-Anchored Membrane Protein Targeting and Insertion

Cited by 103 publications

References 99 publications

Pex19 is involved in importing dually targeted tail‐anchored proteins to both mitochondria and peroxisomes

Pex19 is involved in importing dually targeted tail‐anchored proteins to both mitochondria and peroxisomes

A bacteria-derived tail anchor localizes to peroxisomes in yeast and mammalian cells

Targeting of tail‐anchored proteins to Trichomonas vaginalis hydrogenosomes

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