ArticleThe Journal of cell biology2022
Liquid-liquid phase separation facilitates the biogenesis of secretory storage granules.
Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 64 citations in OpenAlex.
- Spectrin condensates provide a nidus for assembling the axonal membrane-associated periodic skeleton.iScience · 2026Article
- Molecular grammars of predicted intrinsically disordered regions that span the human proteome.Cell · 2026Article
- The Golgi apparatus: adaptations to neuronal shape and functions.The EMBO journal · 2026Review
- Mechanistic insights into cargo sorting and export from the Golgi apparatus.Nature reviews. Molecular cell biology · 2025Review
- Simulations reveal a balance between protein-protein and protein-lipid interactions during condensation on membrane surfaces.Chemical science · 2025Article
- Molecular requirements of chromogranin B for the long-sought anion shunter of regulated secretion.International journal of biological macromolecules · 2025Article
- Extracellular phase separation mediates storage and release of thyroglobulin in the thyroid follicular lumen.Communications biology · 2025Article
- KPNA3 regulates histone locus body formation by modulating condensation and nuclear import of NPAT.The Journal of cell biology · 2025Article
- Skin lamellar bodies: a unique set of lysosome-related organelles.Frontiers in cell and developmental biology · 2025Article
- Secretion of placental peptide hormones: functions and trafficking.Frontiers in endocrinology · 2025Review
- Protein aggregates and biomolecular condensates: implications for human health and disease.Frontiers in molecular biosciences · 2025Review
- Inceptor binds to and directs insulin towards lysosomal degradation in β cells.Nature metabolism · 2024Article
- Liquid-Liquid Phase Separation within Dense-Core Vesicles in Sympathetic Adrenal Chromaffin Cells.Neuroscience bulletin · 2024Article
- Chromogranin B Purification for Condensate Formation and Client Partitioning Assays In Vitro.Bio-protocol · 2024Article
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- A metabolic redox relay supports ER proinsulin export in pancreatic islet β cells.JCI insight · 2024Article
- Protein condensates in the the secretory pathway: Unraveling biophysical interactions and function.Biophysical journal · 2024Review
- A charge-dependent long-ranged force drives tailored assembly of matter in solution.Nature nanotechnology · 2024Article
- Sorting of secretory proteins at theeLife · 2024Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Insulin is synthesized by pancreatic β-cells and stored into secretory granules (SGs). SGs fuse with the plasma membrane in response to a stimulus and deliver insulin to the bloodstream. The mechanism of how proinsulin and its processing enzymes are sorted and targeted from the trans-Golgi network (TGN) to SGs remains mysterious. No cargo receptor for proinsulin has been identified. Here, we show that chromogranin (CG) proteins undergo liquid-liquid phase separation (LLPS) at a mildly acidic pH in the lumen of the TGN, and recruit clients like proinsulin to the condensates. Client selectivity is sequence-independent but based on the concentration of the client molecules in the TGN. We propose that the TGN provides the milieu for converting CGs into a "cargo sponge" leading to partitioning of client molecules, thus facilitating receptor-independent client sorting. These findings provide a new receptor-independent sorting model in β-cells and many other cell types and therefore represent an innovation in the field of membrane trafficking.
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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.