ArticleThe Journal of biological chemistry2013
Proinsulin intermolecular interactions during secretory trafficking in pancreatic β cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Insulin gene mutations and posttranslational and translocation defects: associations with diabetes.Endocrine · 2020Pooled it
- Munc18 binds to and organizes membrane-bound acceptor Q-SNARE complexes in a fashion that depends on the membrane's lipid composition.bioRxiv : the preprint server for biology · 2026Article
- Proinsulin regulators identified with CRISPR screen and in vivo mouse QTL mapping.Nature communications · 2026Article
- Limiting ER-associated degradation capacity triggers acute and chronic effects on insulin biosynthesis.The Journal of clinical investigation · 2026Article
- Rapid protein carbonylation and decreased insulin secretion induced by inflammatory oxidative stress compounds.Free radical biology & medicine · 2026Article
- Secretory stimuli distinctly regulate insulin secretory granule maturation through structural remodeling.Structure (London, England : 1993) · 2025Article
- Article
- A metabolic redox relay supports ER proinsulin export in pancreatic islet β cells.JCI insight · 2024Article
- Membrane lipids couple synaptotagmin to SNARE-mediated granule fusion in insulin-secreting cells.Molecular biology of the cell · 2024Article
- Condensation of the β-cell secretory granule luminal cargoes pro/insulin and ICA512 RESP18 homology domain.Protein science : a publication of the Protein Society · 2023Article
- Synchronized proinsulin trafficking reveals delayed Golgi export accompanies β-cell secretory dysfunction in rodent models of hyperglycemia.Scientific reports · 2023Article
- Understanding Insulin in the Age of Precision Medicine and Big Data: Under-Explored Nature of Genomics.Biomolecules · 2023Review
- Cholesterol Redistribution in Pancreatic β-Cells: A Flexible Path to Regulate Insulin Secretion.Biomolecules · 2023Review
- FK506-Binding Protein 2 Participates in Proinsulin Folding.Biomolecules · 2023Article
- IER3IP1 is critical for maintaining glucose homeostasis through regulating the endoplasmic reticulum function and survival of β cells.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Adaptation to chronic ER stress enforces pancreatic β-cell plasticity.Nature communications · 2022Article
- Coding variants identified in patients with diabetes alter PICK1 BAR domain function in insulin granule biogenesis.The Journal of clinical investigation · 2022Article
- Nutrient Regulation of Pancreatic Islet β-Cell Secretory Capacity and Insulin Production.Biomolecules · 2022Review
- Peptide Model of the Mutant Proinsulin Syndrome. I. Design and Clinical Correlation.Frontiers in endocrinology · 2022Article
- Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Classically, exit from the endoplasmic reticulum (ER) is rate-limiting for secretory protein trafficking because protein folding/assembly occurs there. In this study, we have exploited "hPro-CpepSfGFP," a human proinsulin bearing "superfolder" green fluorescent C-peptide expressed in pancreatic β cells where it is processed to human insulin and CpepSfGFP. Remarkably, steady-state accumulation of hPro-CpepSfGFP and endogenous proinsulin is in the Golgi region, as if final stages of protein folding/assembly were occurring there. The Golgi regional distribution of proinsulin is dynamic, influenced by fasting/refeeding, and increased with β cell zinc deficiency. However, coexpression of ER-entrapped mutant proinsulin-C(A7)Y shifts the steady-state distribution of wild-type proinsulin to the ER. Endogenous proinsulin coprecipitates with hPro-CpepSfGFP and even more so with hProC(A7)Y-CpepSfGFP. Using Cerulean and Venus-tagged proinsulins, we find that both WT-WT and WT-mutant proinsulin pairs exhibit FRET. The data demonstrate that wild-type proinsulin dimerizes within the ER but accumulates at a poorly recognized slow step within the Golgi region, reflecting either slow kinetics of proinsulin hexamerization, steps in formation of nascent secretory granules, or other unknown molecular events. However, in the presence of ongoing misfolding of a subpopulation of proinsulin in β cells, the rate-limiting step in transport of the remaining proinsulin shifts to the ER.
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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.