Protein Homeostasis at the Plasma Membrane

Apaja, Pirjo M.; Lukacs, Gergely L.

doi:10.1152/physiol.00058.2013

Cited by 40 publications

(45 citation statements)

References 154 publications

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“…Our findings build upon related work on the inwardly-rectifying potassium channel Kir2.1 (27), the calcium-gated potassium channel KCa3.1 (96), and the voltage-gated potassium channel hERG (97,98), adding ROMK to a growing list of channels and transporters regulated by post-endocytic transport (99). Previous studies of ROMK in yeast focused instead on the identification of ROMK-interaction partners from human cDNA libraries via the yeast two hybrid (100, 101).…”

Section: Romk Vacuolar Targeting Is Impeded In Yeast Deficient In Escmentioning

confidence: 52%

The endosomal trafficking factors CORVET and ESCRT suppress plasma membrane residence of the renal outer medullary potassium channel (ROMK)

Mackie

Kim

Subramanya

et al. 2018

Journal of Biological Chemistry

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Section: Romk Vacuolar Targeting Is Impeded In Yeast Deficient In Escmentioning

confidence: 52%

The endosomal trafficking factors CORVET and ESCRT suppress plasma membrane residence of the renal outer medullary potassium channel (ROMK)

Mackie

Kim

Subramanya

et al. 2018

Journal of Biological Chemistry

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“…Misfolded proteins cause human diseases as a result of their engagement with protein homeostasis (proteostasis) networks that assess the proteins’ poor quality and target them for degradation [1, 2]. In cystic fibrosis (CF), mutations in the CF transmembrane conductance regulator (CFTR) gene often lead to misfolded CFTR protein that malfunctions [3].…”

Section: Introductionmentioning

confidence: 99%

“…During CFTR translation, multiple chaperones/co-chaperones orchestrate the protein's folding at the endoplasmic reticulum (ER); folding is followed by glycosylation in the Golgi apparatus and trafficking to the cell surface [1, 2]. The most prevalent CFTR mutant is a deletion of phenylalanine at position 508 (ΔF508) that reduces the thermal stability of NBD1 and affects CFTR's interdomain interactions.…”

Section: Introductionmentioning

confidence: 99%

Combination of Correctors Rescues CFTR Transmembrane-Domain Mutants by Mitigating their Interactions with Proteostasis

Lopes‐Pacheco¹,

Boinot²,

Sabirzhanova³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Premature degradation of mutated cystic fibrosis transmembrane conductance regulator (CFTR) protein causes cystic fibrosis (CF), the commonest Mendelian disease in Caucasians. Despite recent advances in precision medicines for CF patients, many CFTR mutants have not been characterized and the effects of these new therapeutic approaches are still unclear for those mutants. Methods: Cells transfected or stably expressing four CFTR transmembrane-domain mutants (G85E, E92K, L1077P, and M1101K) were used to: 1) characterize the mutants according to their protein expression, thermal sensitivity, and degradation pathways; 2) evaluate the effects of correctors in rescuing them; and 3) explore the effects of correctors on CFTR interactions with proteostasis components. Results: All four mutants exhibited lower protein expression than did wild type-CFTR, and they were degraded by proteasomes and aggresomes. At low temperature, only cells expressing the mutants L1077P and M1101K exhibited increased CFTR maturation. Co-administration of C4 and C18 showed the greatest effect, restoring functional expression and partial stability of CFTR bearing E92K, L1077P, or M1101K at the cell surface. However, this treatment was inefficient in rectifying the defect of CFTR bearing G85E. Correctors rescued CFTR mutants by reducing their interactions with proteostasis components associated with protein retention in the endoplasmic reticulum and ubiquitination. Conclusion: Co-administration of C4 and C18 rescued CFTR transmembrane-domain mutants by remodeling the CFTR interactome.

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confidence: 99%

Serum glycomarkers of endoplasmic reticulum and lysosomal-endosomal system stress in human healthy aging and diseases

Pismenetskaya¹,

Butters²

2017

Ukr.Biochem.J.

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To verify the idea that extracellular free oligosaccharides might be able to reflect the functional status of the endoplasmic reticulum (ER) and lysosomal-endosomal system, HPLC-profiles of serum-derived free oligosaccharides (FOS) in human healthyT he multilayered protein quality assurance system encompasses almost all cellular organelles, a network of biochemical processes and a multiplex of intracellular and extracellular signaling cascades [1][2][3][4][5]. At the centre of this wide cellular landscape there are two main hubs -the endoplasmic reticulum (ER) and lysosomal-endosomal system. The former is responsible for quality-reliable guarantee of newly synthesized proteins, the latterfor effective degradation of mature proteins, incorrectly folded proteins and their adducts.The endoplasmic reticulum provides an interconnected space for translation, co-translational and post-translational modifications, folding and assembling of secreted, organelle-targeted and membrane proteins. Only properly folded and assembled proteins can be transported out of the ER via the Golgi apparatus and cytosol to the endpoint of their functional actions -cellular organelles, plasma membrane and extracellular space. Native protein conformation is achieved due to unique environment of the ER lumen and a specific co-translational modification of proteins -N-glycosylation. The oxidation/ reductive conditions of the ER lumen ensure the formation of disulfide bonds maintaining the tertiary and quaternary structure of proteins. The high level of functional chaperone proteins in the ER facilitates protein folding. The high Ca 2+ concentration in the lumen is essential for Ca 2+ -dependent chaperonesprotein interactions. Any disturbance of these three determinants can lead to protein unfolding or misfolding [6].Cells monitor protein folding by a protein quali ty control (QC) system is inbuilt in the ER and

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Protein Homeostasis at the Plasma Membrane

Cited by 40 publications

References 154 publications

The endosomal trafficking factors CORVET and ESCRT suppress plasma membrane residence of the renal outer medullary potassium channel (ROMK)

The endosomal trafficking factors CORVET and ESCRT suppress plasma membrane residence of the renal outer medullary potassium channel (ROMK)

Combination of Correctors Rescues CFTR Transmembrane-Domain Mutants by Mitigating their Interactions with Proteostasis

Serum glycomarkers of endoplasmic reticulum and lysosomal-endosomal system stress in human healthy aging and diseases

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