ArticlePloS one2018
Remodeling the endoplasmic reticulum proteostasis network restores proteostasis of pathogenic GABAA receptors.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Advances regarding the mechanism of endoplasmic reticulum stress in diabetic kidney disease and pharmacological interventions (Review).Molecular medicine reports · 2026Review
- Proteostasis regulation of GABABiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- Pharmacological chaperones restore proteostasis of epilepsy-associated GABAPharmacological research · 2024Article
- Article
- The proteostasis interactomes of trafficking-deficient variants of the voltage-gated potassium channel KThe Journal of biological chemistry · 2024Article
- Adapting the endoplasmic reticulum proteostasis rescues epilepsy-associated NMDA receptor variants.Acta pharmacologica Sinica · 2024Article
- Monitoring the Secretion and Activity of Alpha-1 Antitrypsin in Various Mammalian Cell Types.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Pathogenicity Prediction of GABAbioRxiv : the preprint server for biology · 2023Article
- Pharmacological Analysis of GABAInternational journal of molecular sciences · 2023Article
- Pharmacological chaperones restore proteostasis of epilepsy-associated GABAbioRxiv : the preprint server for biology · 2023Article
- Sustained overexpression of spliced X-box-binding protein-1 in neurons leads to spontaneous seizures and sudden death in mice.Communications biology · 2023Article
- Intermittent hypoxia: linkage between OSAS and epilepsy.Frontiers in pharmacology · 2023Review
- Article
- Secretion of functional α1-antitrypsin is cell type dependent: Implications for intramuscular delivery for gene therapy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Reshaping endoplasmic reticulum quality control through the unfolded protein response.Molecular cell · 2022Review
- Disruption of the Ubiquitin-Proteasome System and Elevated Endoplasmic Reticulum Stress in Epilepsy.Biomedicines · 2022Review
- Nedd4-2 Haploinsufficiency in Mice Impairs the Ubiquitination of Rer1 and Increases the Susceptibility to Endoplasmic Reticulum Stress and Seizures.Frontiers in molecular neuroscience · 2022Article
- Proteostasis Regulators Restore Function of Epilepsy-Associated GABACell chemical biology · 2021Article
- Targeting defective proteostasis in the collagenopathies.Current opinion in chemical biology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Biogenesis of membrane proteins is controlled by the protein homeostasis (proteostasis) network. We have been focusing on protein quality control of γ-aminobutyric acid type A (GABAA) receptors, the major inhibitory neurotransmitter-gated ion channels in mammalian central nervous system. Proteostasis deficiency in GABAA receptors causes loss of their surface expression and thus function on the plasma membrane, leading to epilepsy and other neurological diseases. One well-characterized example is the A322D mutation in the α1 subunit that causes its extensive misfolding and expedited degradation in the endoplasmic reticulum (ER), resulting in autosomal dominant juvenile myoclonic epilepsy. We aimed to correct misfolding of the α1(A322D) subunits in the ER as an approach to restore their functional surface expression. Here, we showed that application of BIX, a specific, potent ER resident HSP70 family protein BiP activator, significantly increases the surface expression of the mutant receptors in human HEK293T cells and neuronal SH-SY5Y cells. BIX attenuates the degradation of α1(A322D) and enhances their forward trafficking and function. Furthermore, because BiP is one major target of the two unfolded protein response (UPR) pathways: ATF6 and IRE1, we continued to demonstrate that modest activations of the ATF6 pathway and IRE1 pathway genetically enhance the plasma membrane trafficking of the α1(A322D) protein in HEK293T cells. Our results underlie the potential of regulating the ER proteostasis network to correct loss-of-function protein conformational diseases.
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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.