ArticleThe Journal of biological chemistry2016
Grp94 Protein Delivers γ-Aminobutyric Acid Type A (GABAA) Receptors to Hrd1 Protein-mediated Endoplasmic Reticulum-associated Degradation.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- GABASynapse (New York, N.Y.) · 2026Review
- Improving Proteostasis of Trafficking-Deficient GABAACS chemical neuroscience · 2025Article
- Proteostasis regulation of GABABiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- Release your inhibitions: The cell biology of GABAergic postsynaptic plasticity.Current opinion in neurobiology · 2025Review
- Pharmacological chaperones restore proteostasis of epilepsy-associated GABAPharmacological research · 2024Article
- Haploinsufficiency of GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- The Essential Functions of Molecular Chaperones and Folding Enzymes in Maintaining Endoplasmic Reticulum Homeostasis.Journal of molecular biology · 2024Review
- Modulating Endoplasmic Reticulum Chaperones and Mutant Protein Degradation in GABRG2(Q390X) Associated with Genetic Epilepsy with Febrile Seizures Plus and Dravet Syndrome.International journal of molecular sciences · 2024Article
- Pathogenicity Prediction of GABAbioRxiv : the preprint server for biology · 2023Article
- The role of molecular chaperones in the mechanisms of epileptogenesis.Cell stress & chaperones · 2023Review
- Identification of EGF Receptor and Thrombospondin-1 as Endogenous Targets of ER-Associated Degradation Enhancer EDEM1 in HeLa Cells.International journal of molecular sciences · 2023Article
- Pharmacological chaperones restore proteostasis of epilepsy-associated GABAbioRxiv : the preprint server for biology · 2023Article
- GRP94 Inhabits the Immortalized Porcine Hepatic Stellate Cells Apoptosis under Endoplasmic Reticulum Stress through Modulating the Expression of IGF-1 and Ubiquitin.International journal of molecular sciences · 2022Article
- Viruses Hijack ERAD to Regulate Their Replication and Propagation.International journal of molecular sciences · 2022Review
- Article
- Pharmacological activation of ATF6 remodels the proteostasis network to rescue pathogenic GABACell & bioscience · 2022Article
- Disruption of the Ubiquitin-Proteasome System and Elevated Endoplasmic Reticulum Stress in Epilepsy.Biomedicines · 2022Review
- Protein quality control ofFrontiers in cellular neuroscience · 2022Review
- Proteostasis Regulators Restore Function of Epilepsy-Associated GABACell chemical biology · 2021Article
- TMT-Based Proteomic Analysis of Plasma from Children with Rolandic Epilepsy.Disease markers · 2020Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Proteostasis maintenance of γ-aminobutyric acid type A (GABAA) receptors dictates their function in controlling neuronal inhibition in mammalian central nervous systems. However, as a multisubunit, multispan, integral membrane protein, even wild type subunits of GABAA receptors fold and assemble inefficiently in the endoplasmic reticulum (ER). Unassembled and misfolded subunits undergo ER-associated degradation (ERAD), but this degradation process remains poorly understood for GABAA receptors. Here, using the α1 subunits of GABAA receptors as a model substrate, we demonstrated that Grp94, a metazoan-specific Hsp90 in the ER lumen, uses its middle domain to interact with the α1 subunits and positively regulates their ERAD. OS-9, an ER-resident lectin, acts downstream of Grp94 to further recognize misfolded α1 subunits in a glycan-dependent manner. This delivers misfolded α1 subunits to the Hrd1-mediated ubiquitination and the valosin-containing protein-mediated extraction pathway. Repressing the initial ERAD recognition step by inhibiting Grp94 enhances the functional surface expression of misfolding-prone α1(A322D) subunits, which causes autosomal dominant juvenile myoclonic epilepsy. This study clarifies a Grp94-mediated ERAD pathway for GABAA receptors, which provides a novel way to finely tune their function in physiological and pathophysiological conditions.
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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.