ArticleProceedings of the National Academy of Sciences of the United States of America2013
βIV-Spectrin and CaMKII facilitate Kir6.2 regulation in pancreatic beta cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Expanding the phenotype of CARS1 variants to include congenital hyperinsulinism.BMC medical genomics · 2025Article
- Tyrosine phosphorylation of Kir6.2 subunit negatively regulates cardiac KBasic research in cardiology · 2025Article
- Phosphoproteomic profiling identifies DNMT1 as a key substrate of beta IV spectrin-dependent ERK/MAPK signaling in suppressing angiogenesis.Biochemical and biophysical research communications · 2024Article
- Using CRISPR-Cas9/phosphoproteomics to identify substrates of calcium/calmodulin-dependent kinase 2δ.The Journal of biological chemistry · 2023Article
- Endothelial tip/stalk cell selection requires BMP9-induced βMolecular biology of the cell · 2023Article
- A Cantú syndrome mutation produces dual effects on KATP channels by disrupting ankyrin B regulation.The Journal of general physiology · 2023Article
- βNature communications · 2022Article
- [Role of CaMK II in pancreatic injury in mice with severe acute pancreatitis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- The phosphatidylserine flippase β-subunit Tmem30a is essential for normal insulin maturation and secretion.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Regulation of Cardiac Conduction and Arrhythmias by Ankyrin/Spectrin-Based Macromolecular Complexes.Journal of cardiovascular development and disease · 2021Review
- The Pancreatic β-Cell: The Perfect Redox System.Antioxidants (Basel, Switzerland) · 2021Review
- The Spread of Spectrin in Ataxia and Neurodegenerative Disease.Journal of experimental neurology · 2021Article
- βIV-Spectrin/STAT3 complex regulates fibroblast phenotype, fibrosis, and cardiac function.JCI insight · 2019Article
- Myocardial death and dysfunction after ischemia-reperfusion injury require CaMKIIδ oxidation.Scientific reports · 2019Article
- STAT3: a link between CaMKII-βIV-spectrin and maladaptive remodeling?The Journal of clinical investigation · 2018Article
- Blockade of the KMolecular psychiatry · 2018Article
- KATP Channels in the Cardiovascular System.Physiological reviews · 2016Review
- Role of CaMKII in cardiac arrhythmias.Trends in cardiovascular medicine · 2015Review
- Use of whole exome sequencing for the identification of Ito-based arrhythmia mechanism and therapy.Journal of the American Heart Association · 2015Article
- Ankyrin-G coordinates intercalated disc signaling platform to regulate cardiac excitability in vivo.Circulation research · 2014Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Identified over a dozen years ago in the brain and pancreatic islet, βIV-spectrin is critical for the local organization of protein complexes throughout the nervous system. βIV-Spectrin targets ion channels and adapter proteins to axon initial segments and nodes of Ranvier in neurons, and βIV-spectrin dysfunction underlies ataxia and early death in mice. Despite advances in βIV-spectrin research in the nervous system, its role in pancreatic islet biology is unknown. Here, we report that βIV-spectrin serves as a multifunctional structural and signaling platform in the pancreatic islet. We report that βIV-spectrin directly associates with and targets the calcium/calmodulin-dependent protein kinase II (CaMKII) in pancreatic islets. In parallel, βIV-spectrin targets ankyrin-B and the ATP-sensitive potassium channel. Consistent with these findings, βIV-spectrin mutant mice lacking CaMKII- or ankyrin-binding motifs display selective loss of expression and targeting of key protein components, including CaMKIIδ. βIV-Spectrin-targeted CaMKII directly phosphorylates the inwardly-rectifying potassium channel, Kir6.2 (alpha subunit of KATP channel complex), and we identify the specific residue, Kir6.2 T224, responsible for CaMKII-dependent regulation of KATP channel function. CaMKII-dependent phosphorylation alters channel regulation resulting in KATP channel inhibition, a cellular phenotype consistent with aberrant insulin regulation. Finally, we demonstrate aberrant KATP channel phosphorylation in βIV-spectrin mutant mice. In summary, our findings establish a broader role for βIV-spectrin in regulation of cell membrane excitability in the pancreatic islet, define the pathway for CaMKII local control in pancreatic beta cells, and identify the mechanism for CaMKII-dependent regulation of KATP channels.
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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.