ArticleThe Biochemical journal2017
Interactions between intersubunit transmembrane domains regulate the chaperone-dependent degradation of an oligomeric membrane protein.
Article in The Biochemical journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Excess dietary sodium restores electrolyte and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron.American journal of physiology. Renal physiology · 2025Article
- Article
- Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum function.Molecular biology of the cell · 2024Article
- Excess dietary sodium partially restores salt and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron.bioRxiv : the preprint server for biology · 2024Article
- Dosage suppressors of gpn2ts mutants and functional insights into the role of Gpn2 in budding yeast.PloS one · 2024Article
- Lhs1 dependent ERAD is determined by transmembrane domain context.The Biochemical journal · 2023Article
- Signal sequences encode information for protein folding in the endoplasmic reticulum.The Journal of cell biology · 2023Article
- The molecular chaperone GRP170 protects against ER stress and acute kidney injury in mice.JCI insight · 2022Article
- Paraoxonase 2 is an ER chaperone that regulates the epithelial NaAmerican journal of physiology. Cell physiology · 2022Article
- Paraoxonase 3 functions as a chaperone to decrease functional expression of the epithelial sodium channel.The Journal of biological chemistry · 2020Article
- Hsp104 facilitates the endoplasmic-reticulum-associated degradation of disease-associated and aggregation-prone substrates.Protein science : a publication of the Protein Society · 2019Article
- Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.Chemical reviews · 2019Article
- Thumb domains of the three epithelial NaThe Journal of biological chemistry · 2018Article
- SPLUNC1 is an allosteric modulator of the epithelial sodium channel.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- N-linked glycans are required on epithelial NaAmerican journal of physiology. Renal physiology · 2018Article
- Remodeling the endoplasmic reticulum proteostasis network restores proteostasis of pathogenic GABAA receptors.PloS one · 2018Article
- Regulation of the epithelial NaThe Journal of biological chemistry · 2017Article
- Transmembrane helix hydrophobicity is an energetic barrier during the retrotranslocation of integral membrane ERAD substrates.Molecular biology of the cell · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
In the kidney, the epithelial sodium channel (ENaC) regulates blood pressure through control of sodium and volume homeostasis, and in the lung, ENaC regulates the volume of airway and alveolar fluids. ENaC is a heterotrimer of homologous α-, β- and γ-subunits, and assembles in the endoplasmic reticulum (ER) before it traffics to and functions at the plasma membrane. Improperly folded or orphaned ENaC subunits are subject to ER quality control and targeted for ER-associated degradation (ERAD). We previously established that a conserved, ER lumenal, molecular chaperone, Lhs1/GRP170, selects αENaC, but not β- or γ-ENaC, for degradation when the ENaC subunits were individually expressed. We now find that when all three subunits are co-expressed, Lhs1-facilitated ERAD was blocked. To determine which domain-domain interactions between the ENaC subunits are critical for chaperone-dependent quality control, we employed a yeast model and expressed chimeric α/βENaC constructs in the context of the ENaC heterotrimer. We discovered that the βENaC transmembrane domain was sufficient to prevent the Lhs1-dependent degradation of the α-subunit in the context of the ENaC heterotrimer. Our work also found that Lhs1 delivers αENaC for proteasome-mediated degradation after the protein has become polyubiquitinated. These data indicate that the Lhs1 chaperone selectively recognizes an immature form of αENaC, one which has failed to correctly assemble with the other channel subunits via its transmembrane domain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.