The Protein Targeting Factor Get3 Functions as ATP-Independent Chaperone under Oxidative Stress Conditions

Voth, Wilhelm; Schick, Markus; Gates, S.N.; Sheng, Li; Vilardi, Fabio; Gostimskaya, Irina; Southworth, Daniel R.; Schwappach, Blanche; Jakob, Ursula

doi:10.1016/j.molcel.2014.08.017

Cited by 68 publications

(129 citation statements)

References 40 publications

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“…S7A). No cytosolic aggregates or increased fluorescence foci were visible in the cytoplasm, which was reminiscent of findings in yeast get pathway KOs (15,43). However, we repeatedly observed differences in GFP signal under identical conditions and settings.…”

Section: Loss Of the Get Pathway Leads To Reduced Protein Levels Of Ssupporting

confidence: 83%

“…Lastly, the AtGET3a foci that can occur in cells of mutant plants (but never in the WT background) (Fig. 5D) and that are similar to aggregates observed in stressed yeast cells (43) suggest additional functions of AtGET3a that nonetheless depend on AtGET1. The aggregate-like structures were not found in all cells of mutant plants, suggesting a dosagedependent effect (i.e., if levels of AtGET3a-GFP exceed a certain threshold, clustering occurs).…”

Section: Discussionmentioning

confidence: 75%

“…5D, Left and Movie S2). Foci may be a result of clustering of uninserted TA proteins with multimers of AtGET3a, similar to effects observed in yeast Δget1 KOs (43,45). We have also analyzed expression of Boxplot as in Fig.…”

Section: Loss Of the Get Pathway Leads To Reduced Protein Levels Of Smentioning

confidence: 75%

“…S1B)-have evolved as organellar chaperones with putative thiol-disulfide oxidoreductase function and lost (or never had) the TA insertion capability, whereas GET3a orthologs maintained (or acquired) both functions. Notably, the chaperone function of ScGET3 is ATP-independent, whereas TA-insertase activity depends on ATP (43). A version of AtGET3a, where the ATPase motif is mutated (G28A), fails to rescue the root hair growth phenotype (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to the CxxC motif, the CVC motif can be found in all eukaryotic GET3a orthologs that we analyzed. Nevertheless, the CxxC motif is required for ScGET3 to act as a general chaperone under oxidative stress conditions, binding unfolded proteins and preventing their aggregation (43,45). Hence, it is conceivable that GET3bc paralogs-that feature CxxC (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Loss of GET pathway orthologs in Arabidopsis thaliana causes root hair growth defects and affects SNARE abundance

Xing

Mehlhorn

Wallmeroth

et al. 2017

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

109

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Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are key players in cellular trafficking and coordinate vital cellular processes, such as cytokinesis, pathogen defense, and ion transport regulation. With few exceptions, SNAREs are tail-anchored (TA) proteins, bearing a C-terminal hydrophobic domain that is essential for their membrane integration. Recently, the Guided Entry of Tail-anchored proteins (GET) pathway was described in mammalian and yeast cells that serve as a blueprint of TA protein insertion [Schuldiner M, et al. (2008) Cell 134(4):634-645; Stefanovic S, Hegde RS (2007) Cell 128(6):1147-1159]. This pathway consists of six proteins, with the cytosolic ATPase GET3 chaperoning the newly synthesized TA protein posttranslationally from the ribosome to the endoplasmic reticulum (ER) membrane. Structural and biochemical insights confirmed the potential of pathway components to facilitate membrane insertion, but the physiological significance in multicellular organisms remains to be resolved. Our phylogenetic analysis of 37 GET3 orthologs from 18 different species revealed the presence of two different GET3 clades. We identified and analyzed GET pathway components in Arabidopsis thaliana and found reduced root hair elongation in Atget lines, possibly as a result of reduced SNARE biogenesis. Overexpression of AtGET3a in a receptor knockout (KO) results in severe growth defects, suggesting presence of alternative insertion pathways while highlighting an intricate involvement for the GET pathway in cellular homeostasis of plants.GET pathway | TA proteins | SNAREs | ER membrane | root hairs

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Section: Loss Of the Get Pathway Leads To Reduced Protein Levels Of Ssupporting

confidence: 83%

Section: Discussionmentioning

confidence: 75%

Section: Loss Of the Get Pathway Leads To Reduced Protein Levels Of Smentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Loss of GET pathway orthologs in Arabidopsis thaliana causes root hair growth defects and affects SNARE abundance

Xing

Mehlhorn

Wallmeroth

et al. 2017

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

109

View full text Add to dashboard Cite

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Membrane Insertion of Tail‐anchored Proteins

Borgese

2015

Encyclopedia of Life Sciences

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Tail‐anchored proteins are a special class of transmembrane proteins, consisting of a cytosolic domain anchored to the phospholipid bilayer by a single hydrophobic segment adjacent to their most C‐terminus. Because of their particular topology, the C‐terminal anchor must be inserted into membranes post‐translationally by mechanisms that differ from the well‐known targeting/translocation co‐translational pathway. Recently, several advances have created a new understanding of the tail‐anchored protein insertion machinery. Because of the essential cellular roles carried out by tail‐anchored proteins, including vesicle fusion, regulation of apoptosis and formation of interorganellar contact sites, uncovering the machinery responsible for their biogenesis should further our ability to understand a wide variety of diseases such as forms of cancer caused by activation of the tail‐anchored protein oncogene BCL2. Key Concepts Tail‐anchored proteins have C‐terminal hydrophobic domains. Tail‐anchored proteins are inserted post‐translationally into the membrane. The GET complex inserts tail‐anchored proteins into the endoplasmic reticulum membrane in yeast. The TRC complex chaperones tail‐anchored proteins into endoplasmic reticulum membranes in mammals. The mitochondrial outer membrane appears to be the preferred destination of tail‐anchored proteins that fail to engage the GET/TRC complex. Functions of the GET/TRC pathway additional to tail‐anchored protein targeting are presently under intense investigation.

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The effects of neutrophil-generated hypochlorous acid and other hypohalous acids on host and pathogens

Ulfig

Leichert

2020

Cell. Mol. Life Sci.

151

132

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Neutrophils are predominant immune cells that protect the human body against infections by deploying sophisticated antimicrobial strategies including phagocytosis of bacteria and neutrophil extracellular trap (NET) formation. Here, we provide an overview of the mechanisms by which neutrophils kill exogenous pathogens before we focus on one particular weapon in their arsenal: the generation of the oxidizing hypohalous acids HOCl, HOBr and HOSCN during the so-called oxidative burst by the enzyme myeloperoxidase. We look at the effects of these hypohalous acids on biological systems in general and proteins in particular and turn our attention to bacterial strategies to survive HOCl stress. HOCl is a strong inducer of protein aggregation, which bacteria can counteract by chaperone-like holdases that bind unfolding proteins without the need for energy in the form of ATP. These chaperones are activated by HOCl through thiol oxidation (Hsp33) or N-chlorination of basic amino acid side-chains (RidA and CnoX) and contribute to bacterial survival during HOCl stress. However, neutrophil-generated hypohalous acids also affect the host system. Recent studies have shown that plasma proteins act not only as sinks for HOCl, but get actively transformed into modulators of the cellular immune response through N-chlorination. N-chlorinated serum albumin can prevent aggregation of proteins, stimulate immune cells, and act as a pro-survival factor for immune cells in the presence of cytotoxic antigens. Finally, we take a look at the emerging role of HOCl as a potential signaling molecule, particularly its role in neutrophil extracellular trap formation.

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The Protein Targeting Factor Get3 Functions as ATP-Independent Chaperone under Oxidative Stress Conditions

Cited by 68 publications

References 40 publications

Loss of GET pathway orthologs in Arabidopsis thaliana causes root hair growth defects and affects SNARE abundance

Loss of GET pathway orthologs in Arabidopsis thaliana causes root hair growth defects and affects SNARE abundance

Membrane Insertion of Tail‐anchored Proteins

The effects of neutrophil-generated hypochlorous acid and other hypohalous acids on host and pathogens

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