ArticleThe Journal of biological chemistry2011
Conserved intramolecular disulfide bond is critical to trafficking and fate of ATP-binding cassette (ABC) transporters ABCB6 and sulfonylurea receptor 1 (SUR1)/ABCC8.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Genetic and clinical insights into acute kidney injury in maturity-onset diabetes of the young caused by theExperimental and therapeutic medicine · 2025Article
- Article
- The role of ATP-binding Cassette subfamily B member 6 in the inner ear.Nature communications · 2024Article
- Cryo-EM structure of cadmium-bound human ABCB6.Communications biology · 2024Article
- Folding correctors can restore CFTR posttranslational folding landscape by allosteric domain-domain coupling.Nature communications · 2023Article
- KFrontiers in endocrinology · 2023Review
- Structural Insights into Porphyrin Recognition by the Human ATP-Binding Cassette Transporter ABCB6.Molecules and cells · 2022Article
- Subcellular trafficking and endocytic recycling of KAmerican journal of physiology. Cell physiology · 2022Review
- The NRF2/KEAP1 Axis in the Regulation of Tumor Metabolism: Mechanisms and Therapeutic Perspectives.Biomolecules · 2020Review
- Linker Domains: Why ABC Transporters 'Live in Fragments no Longer'.Trends in biochemical sciences · 2020Review
- Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases.Nature reviews. Drug discovery · 2019Review
- ABCB6, an ABC Transporter Impacting Drug Response and Disease.The AAPS journal · 2017Review
- Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating.eLife · 2017Article
- Pharmacological Correction of Trafficking Defects in ATP-sensitive Potassium Channels Caused by Sulfonylurea Receptor 1 Mutations.The Journal of biological chemistry · 2016Article
- The severity of hereditary porphyria is modulated by the porphyrin exporter and Lan antigen ABCB6.Nature communications · 2016Article
- Identification of a Disulfide Bridge in Sodium-Coupled Neutral Amino Acid Transporter 2(SNAT2) by Chemical Modification.PloS one · 2016Article
- Role of the N-terminal transmembrane domain in the endo-lysosomal targeting and function of the human ABCB6 protein.The Biochemical journal · 2015Article
- Where is it and How Does it Get There - Intracellular Localization and Traffic of P-glycoprotein.Frontiers in oncology · 2013Review
- Pharmacological rescue of trafficking-impaired ATP-sensitive potassium channels.Frontiers in physiology · 2013Review
- Crucial role for phylogenetically conserved cytoplasmic loop 3 in ABCC4 protein expression.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
The ATP-binding cassette (ABC) transporter ABCB6 is a mitochondrial porphyrin transporter that activates porphyrin biosynthesis. ABCB6 lacks a canonical mitochondrial targeting sequence but reportedly traffics to other cellular compartments such as the plasma membrane. How ABCB6 reaches these destinations is unknown. In this study, we show that endogenous ABCB6 is glycosylated in multiple cell types, indicating trafficking through the endoplasmic reticulum (ER), and has only one atypical site for glycosylation (NXC) in its amino terminus. ABCB6 remained glycosylated when the highly conserved cysteine (Cys-8) was substituted with serine to make a consensus site, NXS. However, this substitution blocked ER exit and produced ABCB6 degradation, which was mostly reversed by the proteasomal inhibitor MG132. The amino terminus of ABCB6 has an additional highly conserved ER luminal cysteine (Cys-26). When Cys-26 was mutated alone or in combination with Cys-8, it also resulted in instability and ER retention. Further analysis revealed that these two cysteines form a disulfide bond. We discovered that other ABC transporters with an amino terminus in the ER had similarly configured conserved cysteines. This analysis led to the discovery of a disease-causing mutation in the sulfonylurea receptor 1 (SUR1)/ABCC8 from a patient with hyperinsulinemic hypoglycemia. The mutant allele only contains a mutation in a conserved amino-terminal cysteine, producing SUR1 that fails to reach the cell surface. These results suggest that for ABC transporters the propensity to form a disulfide bond in the ER defines a unique checkpoint that determines whether a protein is ER-retained.
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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.