ArticleMolecular biology of the cell2000
Endoplasmic reticulum quality control of oligomeric membrane proteins: topogenic determinants involved in the degradation of the unassembled Na,K-ATPase alpha subunit and in its stabilization by beta subunit assembly.
Article in Molecular biology of the cell, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Enhanced recovery after surgery in gastric cancer surgery: Systematic review and meta-analysis of perioperative indwelling drainage tube use.World journal of gastrointestinal surgery · 2025Article
- Na,K-ATPase Expression Can Be Limited Post-Transcriptionally: A Test of the Role of the Beta Subunit, and a Review of Evidence.International journal of molecular sciences · 2024Review
- Lhs1 dependent ERAD is determined by transmembrane domain context.The Biochemical journal · 2023Article
- NaMolecules (Basel, Switzerland) · 2021Review
- Assistance for Folding of Disease-Causing Plasma Membrane Proteins.Biomolecules · 2020Review
- Article
- The Physiology of the Gastric Parietal Cell.Physiological reviews · 2020Review
- Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.Chemical reviews · 2019Article
- Targeting β2 subunit of NaAmerican journal of cancer research · 2019Article
- Transmembrane helix hydrophobicity is an energetic barrier during the retrotranslocation of integral membrane ERAD substrates.Molecular biology of the cell · 2017Article
- Interactions between intersubunit transmembrane domains regulate the chaperone-dependent degradation of an oligomeric membrane protein.The Biochemical journal · 2017Article
- Trafficking to the apical and basolateral membranes in polarized epithelial cells.Journal of the American Society of Nephrology : JASN · 2014Review
- Functional analysis of human Na(+)/K(+)-ATPase familial or sporadic hemiplegic migraine mutations expressed in Xenopus oocytes.World journal of biological chemistry · 2014Article
- MicroRNAs contribute to the maintenance of cell-type-specific physiological characteristics: miR-192 targets Na+/K+-ATPase β1.Nucleic acids research · 2013Article
- N-myc downstream-regulated gene 2, a novel estrogen-targeted gene, is involved in the regulation of Na+/K+-ATPase.The Journal of biological chemistry · 2011Article
- Saccharomyces cerivisiae as a model system for kidney disease: what can yeast tell us about renal function?American journal of physiology. Renal physiology · 2011Article
- Regulation of Na,K-ATPase subunit abundance by translational repression.The Journal of biological chemistry · 2009Article
- Sodium-potassium ATPase 1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stress.Human molecular genetics · 2008Article
- The beta subunit of the Na+/K+-ATPase follows the conformational state of the holoenzyme.The Journal of general physiology · 2005Article
- Conserved ERAD-like quality control of a plant polytopic membrane protein.The Plant cell · 2005Article
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4 authors.
Funding
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Abstract
The molecular nature of determinants that mediate degradation of unassembled, polytopic subunits of oligomeric membrane proteins and their stabilization after partner subunit assembly is largely unknown. Expressing truncated Na,K-ATPase alpha subunits alone or together with beta subunits, we find that in unassembled alpha subunits neither the four N-terminal transmembrane segments acting as efficient alternating signal anchor-stop transfer sequences nor the large, central cytoplasmic loop exposes any degradation signal, whereas poor membrane insertion efficiency of C-terminal membrane domains M5, M7, and M9 coincides with the transient exposure of degradation signals to the cytoplasmic side. beta assembly with an alpha domain comprising at least D902 up to Y910 in the extracytoplasmic M7/M8 loop is necessary to stabilize Na,K-ATPase alpha subunits by favoring M7/M8 membrane pair formation and by protecting a degradation signal recognized from the endoplasmic reticulum (ER) lumenal side. Thus our results suggest that ER degradation of Na,K-ATPase alpha subunits is 1) mainly mediated by folding defects caused by inefficient membrane insertion of certain membrane domains, 2) a multistep process, which involves proteolytic and/or chaperone components acting from the ER lumenal side in addition to cytosolic, proteasome-related factors, and 3) prevented by partner subunit assembly because of direct protection and retrieval of degradation signals from the cytoplasm to the ER lumenal side. These results likely represent a paradigm for the ER quality control of unassembled, polytopic subunits of oligomeric membrane proteins.
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