ArticleMolecular biology of the cell2010
Role of Hsp90 in biogenesis of the beta-cell ATP-sensitive potassium channel complex.
Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 40 citations in OpenAlex.
- Heat shock protein 90 inhibitors reduce trafficking of ATP-gated P2X1 receptors and human platelet responsiveness.The Journal of biological chemistry · 2012Trial
- Marked oestrous cycle-dependent regulation of rat arterial KBritish journal of pharmacology · 2023Article
- Role of upregulation of the KAging cell · 2022Article
- Kir Channel Molecular Physiology, Pharmacology, and Therapeutic Implications.Handbook of experimental pharmacology · 2021Review
- Production and purification of ATP-sensitive potassium channel particles for cryo-electron microscopy.Methods in enzymology · 2021Article
- Pharmacological chaperones of ATP-sensitive potassium channels: Mechanistic insight from cryoEM structures.Molecular and cellular endocrinology · 2020Review
- Chaperoning Endoplasmic Reticulum-Associated Degradation (ERAD) and Protein Conformational Diseases.Cold Spring Harbor perspectives in biology · 2019Review
- Enteroviral infections in the pathogenesis of type 1 diabetes: new insights for therapeutic intervention.Current opinion in pharmacology · 2018Review
- Angiotensin II Promotes KHypertension (Dallas, Tex. : 1979) · 2018Article
- Anticancer Pyrroloquinazoline LBL1 Targets Nuclear Lamins.ACS chemical biology · 2018Article
- The expression of KAnnals of translational medicine · 2018Article
- Natural Killer Cell Evasion Is Essential for Infection by Rhesus Cytomegalovirus.PLoS pathogens · 2016Article
- Long-term in vivo polychlorinated biphenyl 126 exposure induces oxidative stress and alters proteomic profile on islets of Langerhans.Scientific reports · 2016Article
- Structurally distinct ligands rescue biogenesis defects of the KATP channel complex via a converging mechanism.The Journal of biological chemistry · 2015Article
- Overproduction and biophysical characterization of human HSP70 proteins.Protein expression and purification · 2015Article
- Glutaredoxin 2 (Grx2) gene deletion induces early onset of age-dependent cataracts in mice.The Journal of biological chemistry · 2014Article
- Monoubiquitination is critical for ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (Otub1) to suppress UbcH5 enzyme and stabilize p53 protein.The Journal of biological chemistry · 2014Article
- Pharmacological rescue of trafficking-impaired ATP-sensitive potassium channels.Frontiers in physiology · 2013Review
- How early studies on secreted and membrane protein quality control gave rise to the ER associated degradation (ERAD) pathway: the early history of ERAD.Biochimica et biophysica acta · 2013Review
- The TCF7L2 rs7903146 (T) allele is associated with type 2 diabetes in urban Ghana: a hospital-based case-control study.BMC medical genetics · 2013Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The pancreatic beta-cell ATP-sensitive potassium (K(ATP)) channel is a multimeric protein complex composed of four inwardly rectifying potassium channel (Kir6.2) and four sulfonylurea receptor 1 (SUR1) subunits. K(ATP) channels play a key role in glucose-stimulated insulin secretion by linking glucose metabolism to membrane excitability. Many SUR1 and Kir6.2 mutations reduce channel function by disrupting channel biogenesis and processing, resulting in insulin secretion disease. To better understand the mechanisms governing K(ATP) channel biogenesis, a proteomics approach was used to identify chaperone proteins associated with K(ATP) channels. We report that chaperone proteins heat-shock protein (Hsp)90, heat-shock cognate protein (Hsc)70, and Hsp40 are associated with beta-cell K(ATP) channels. Pharmacologic inhibition of Hsp90 function by geldanamycin reduces, whereas overexpression of Hsp90 increases surface expression of wild-type K(ATP) channels. Coimmunoprecipitation data indicate that channel association with the Hsp90 complex is mediated through SUR1. Accordingly, manipulation of Hsp90 protein expression or function has significant effects on the biogenesis efficiency of SUR1, but not Kir6.2, expressed alone. Interestingly, overexpression of Hsp90 selectively improved surface expression of mutant channels harboring a subset of disease-causing SUR1 processing mutations. Our study demonstrates that Hsp90 regulates biogenesis efficiency of heteromeric K(ATP) channels via SUR1, thereby affecting functional expression of the channel in beta-cell membrane.
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