ArticlePLoS biology2013
PICK1 and ICA69 control insulin granule trafficking and their deficiencies lead to impaired glucose tolerance.
Article in PLoS biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 93 citations in OpenAlex.
- Epigenetic landscapes in human pancreatic islets reveal distinct drivers for adaptation to age and type 2 diabetes.Nature communications · 2026Article
- Targeted proteomics reveals immune protein patterns in serum from patients with calcific aortic stenosis.iScience · 2025Article
- Molecular Portrait of Autoantigens in Type 1 Diabetes.Biomolecules · 2025Review
- Circulating IFNγ-associated protein signatures predict response to neoadjuvant immunotherapy in patients with stage III melanoma.Cancer cell international · 2025Article
- Optimized Proteomic Analysis of Insulin Granules From MIN6 Cells Identifies Scamp3, a Novel Regulator of Insulin Secretion and Content.Diabetes · 2024Article
- Sodium arsenite induces aggresome formation by promoting PICK1 BAR domain homodimer formation.Molecular biology of the cell · 2024Article
- Peripherally restricted PICK1 inhibitor mPD5 ameliorates pain behaviors in murine inflammatory and neuropathic pain models.JCI insight · 2024Article
- RFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function.Diabetologia · 2024Article
- Long-read and short-read RNA-seq reveal the transcriptional regulation characteristics ofAnimal reproduction · 2024Article
- Multi-omics study identifies that PICK1 deficiency causes male infertility by inhibiting vesicle trafficking in Sertoli cells.Reproductive biology and endocrinology : RB&E · 2023Article
- 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
- PICK1-Deficient Mice Maintain Their Glucose Tolerance During Diet-Induced Obesity.Journal of the Endocrine Society · 2023Article
- Secretory autophagy promotes RAB37-mediated insulin secretion under glucose stimulation bothAutophagy · 2023Article
- Identification of the functional domain of the dense core vesicle biogenesis factor HID-1.PloS one · 2023Article
- ICA69 regulates activity-dependent synaptic strengthening and learning and memory.Frontiers in molecular neuroscience · 2023Article
- Trafficking of hormones and trophic factors to secretory and extracellular vesicles: a historical perspective and new hypothesis.Extracellular vesicles and circulating nucleic acids · 2023Article
- Inflammatory Cytokines Rewire the Proinsulin Interaction Network in Human Islets.The Journal of clinical endocrinology and metabolism · 2022Article
- Review
- Coding variants identified in patients with diabetes alter PICK1 BAR domain function in insulin granule biogenesis.The Journal of clinical investigation · 2022Article
- The adaptor protein PICK1 targets the sorting receptor SorLA.Molecular brain · 2022Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetes is a metabolic disorder characterized by hyperglycemia. Insulin, which is secreted by pancreatic beta cells, is recognized as the critical regulator of blood glucose, but the molecular machinery responsible for insulin trafficking remains poorly defined. In particular, the roles of cytosolic factors that govern the formation and maturation of insulin granules are unclear. Here we report that PICK1 and ICA69, two cytosolic lipid-binding proteins, formed heteromeric BAR-domain complexes that associated with insulin granules at different stages of their maturation. PICK1-ICA69 heteromeric complexes associated with immature secretory granules near the trans-Golgi network (TGN). A brief treatment of Brefeldin A, which blocks vesicle budding from the Golgi, increased the amount of PICK1 and ICA69 at TGN. On the other hand, mature secretory granules were associated with PICK1 only, not ICA69. PICK1 deficiency in mice caused the complete loss of ICA69 and led to increased food and water intake but lower body weight. Glucose tolerance tests demonstrated that these mutant mice had high blood glucose, a consequence of insufficient insulin. Importantly, while the total insulin level was reduced in PICK1-deficient beta cells, proinsulin was increased. Lastly, ICA69 knockout mice also displayed similar phenotype as the mice deficient in PICK1. Together, our results indicate that PICK1 and ICA69 are key regulators of the formation and maturation of insulin granules.
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