ArticleProceedings of the National Academy of Sciences of the United States of America2008
Role of furin in granular acidification in the endocrine pancreas: identification of the V-ATPase subunit Ac45 as a candidate substrate.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 81 citations in OpenAlex.
- Granular Cell Dermatofibroma Demonstrates Loss-of-Function Mutations in V-ATPase Component Genes.Journal of cutaneous pathology · 2026Article
- Molecular analysis of long COVID and new-onset diabetes mellitus: pathobiological relationships and current mechanistic views.Frontiers in endocrinology · 2025Review
- Big1 is a newly identified autophagy regulator that is critical for a fully functional V-ATPase.Molecular biology of the cell · 2024Article
- Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells.Viruses · 2024Review
- ATP6AP2, a regulator of LRP6/β-catenin protein trafficking, promotes Wnt/β-catenin signaling and bone formation in a cell type dependent manner.Bone research · 2024Article
- The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb.Cell research · 2024Article
- Review
- The emerging role of furin in neurodegenerative and neuropsychiatric diseases.Translational neurodegeneration · 2022Review
- Going viral in the islet: mediators of SARS-CoV-2 entry beyond ACE2.Journal of molecular endocrinology · 2022Review
- Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors.International journal of molecular sciences · 2022Article
- Review
- The Role of Proteases and Serpin Protease Inhibitors in β-Cell Biology and Diabetes.Biomolecules · 2022Review
- Article
- Inside the Insulin Secretory Granule.Metabolites · 2021Review
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- Inhibition of furin by bone targeting superparamagnetic iron oxide nanoparticles alleviated breast cancer bone metastasis.Bioactive materials · 2021Article
- COVID-19 disease and malignant cancers: The impact for theInternational journal of biological sciences · 2021Article
- Association Between Serum Furin and Fasting Glucose: A Cross-Sectional Study in Chinese Adults.Frontiers in endocrinology · 2021Article
- Determination of secretory granule maturation times in pancreatic islet β-cells by serial block-face electron microscopy.Journal of structural biology · 2020Article
- Cryo-EM structures of intact V-ATPase from bovine brain.Nature communications · 2020Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Furin is a proprotein convertase which activates a variety of regulatory proteins in the constitutive exocytic and endocytic pathway. The effect of genetic ablation of fur was studied in the endocrine pancreas to define its physiological function in the regulated secretory pathway. Pdx1-Cre/loxP furin KO mice show decreased secretion of insulin and impaired processing of known PC2 substrates like proPC2 and proinsulin II. Both secretion and PC2 activity depend on granule acidification, which was demonstrated to be significantly decreased in furin-deficient beta cells by using the acidotrophic agent 3-(2,4-dinitroanilino)-3'amino-N-methyldipropylamine (DAMP). Ac45, an accessory subunit of the proton pump V-ATPase, was investigated as a candidate substrate. Ac45 is highly expressed in islets of Langerhans and furin was able to cleave Ac45 ex vivo. Furthermore, the exact cleavage site was determined. In addition, reduced regulated secretion and proinsulin II processing could be obtained in the insulinoma cell line betaTC3 by downregulation of either furin or Ac45. Together, these data establish an important role for furin in regulated secretion, particularly in intragranular acidification most likely due to impaired processing of Ac45.
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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 Socratic graph.