ArticleMolecular cell2019
Cells Deploy a Two-Pronged Strategy to Rectify Misfolded Proinsulin Aggregates.
Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Revisiting Inherited Metabolic Diseases (IMDs) Through the Lens of Selective Autophagy.Journal of inherited metabolic disease · 2026Review
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Coordinated expression and assembly of BiP, p58Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- ER-phagy receptors: structural mechanisms in selective ER degradation and disease implications.Acta pharmacologica Sinica · 2026Review
- XIAP Stabilizes DDRGK1 to Promote ER-Phagy and Protects Against Noise-Induced Hearing Loss.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Biomolecular Condensates in and Around the ER-Golgi Interface.Sub-cellular biochemistry · 2026Review
- Autophagy, ER-phagy and ER Dynamics During Cell Differentiation.Journal of molecular biology · 2025Review
- Endoplasmic reticulum (ER) protein degradation by ER-associated degradation and ER-phagy.Trends in cell biology · 2025Review
- Coordinated Role of Autophagy and ERAD in Maintaining Neuroendocrine Function by Preventing Prohormone Aggregation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Less is better: various means to reduce protein load in the endoplasmic reticulum.The FEBS journal · 2025Review
- Exploring proinsulin proteostasis: insights into beta cell health and diabetes.Frontiers in molecular biosciences · 2025Review
- Protein aggregates and biomolecular condensates: implications for human health and disease.Frontiers in molecular biosciences · 2025Review
- Reticulophagy and viral infection.Autophagy · 2025Review
- PINK1 controls RTN3L-mediated ER autophagy by regulating peripheral tubule junctions.The Journal of cell biology · 2024Article
- RTN3L and CALCOCO1 function in parallel to maintain proteostasis in the endoplasmic reticulum.Autophagy · 2024Article
- Time-resolved interactome profiling deconvolutes secretory protein quality control dynamics.Molecular systems biology · 2024Article
- Sestrin2 drives ER-phagy in response to protein misfolding.Developmental cell · 2024Article
- The Essential Functions of Molecular Chaperones and Folding Enzymes in Maintaining Endoplasmic Reticulum Homeostasis.Journal of molecular biology · 2024Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin gene coding sequence mutations are known to cause mutant INS-gene-induced diabetes of youth (MIDY), yet the cellular pathways needed to prevent misfolded proinsulin accumulation remain incompletely understood. Here, we report that Akita mutant proinsulin forms detergent-insoluble aggregates that entrap wild-type (WT) proinsulin in the endoplasmic reticulum (ER), thereby blocking insulin production. Two distinct quality-control mechanisms operate together to combat this insult: the ER luminal chaperone Grp170 prevents proinsulin aggregation, while the ER membrane morphogenic protein reticulon-3 (RTN3) disposes of aggregates via ER-coupled autophagy (ER-phagy). We show that enhanced RTN-dependent clearance of aggregated Akita proinsulin helps to restore ER export of WT proinsulin, which can promote WT insulin production, potentially alleviating MIDY. We also find that RTN3 participates in the clearance of other mutant prohormone aggregates. Together, these results identify a series of substrates of RTN3-mediated ER-phagy, highlighting RTN3 in the disposal of pathogenic prohormone aggregates.
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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.