ArticleThe Journal of biological chemistry2008
Regulation of insulin granule turnover in pancreatic beta-cells by cleaved ICA512.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Molecular Portrait of Autoantigens in Type 1 Diabetes.Biomolecules · 2025Review
- Insulin granule morphology and crinosome formation in mice lacking the pancreatic β cell-specific phogrin (PTPRN2) gene.Histochemistry and cell biology · 2024Article
- Affinity purification of serum-derived anti-IA-2 autoantibodies in type 1 diabetes using a novel MBP-IA-2 fusion protein.Biochemistry and biophysics reports · 2023Article
- A mutant α1antitrypsin in complex with heat shock proteins as the primary antigen in type 1 diabetes in silico investigation.Scientific reports · 2021Article
- ICA512 RESP18 homology domain is a protein-condensing factor and insulin fibrillation inhibitor.The Journal of biological chemistry · 2019Article
- Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.Physiological reviews · 2018Review
- A Global Approach for Quantitative Super Resolution and Electron Microscopy on Cryo and Epoxy Sections Using Self-labeling Protein Tags.Scientific reports · 2017Article
- Novel prokaryotic expression of thioredoxin-fused insulinoma associated protein tyrosine phosphatase 2 (IA-2), its characterization and immunodiagnostic application.BMC biotechnology · 2016Article
- The p21-activated kinase (PAK1) is involved in diet-induced beta cell mass expansion and survival in mice and human islets.Diabetologia · 2016Article
- The F-actin modifier villin regulates insulin granule dynamics and exocytosis downstream of islet cell autoantigen 512.Molecular metabolism · 2016Article
- Islet Autoantibodies.Current diabetes reports · 2016Review
- Stability of proICA512/IA-2 and its targeting to insulin secretory granules require β4-sheet-mediated dimerization of its ectodomain in the endoplasmic reticulum.Molecular and cellular biology · 2015Article
- X-ray structure of the mature ectodomain of phogrin.Journal of structural and functional genomics · 2015Article
- Human fibrocytes express multiple antigens associated with autoimmune endocrine diseases.The Journal of clinical endocrinology and metabolism · 2014Article
- Syntrophin proteins as Santa Claus: role(s) in cell signal transduction.Cellular and molecular life sciences : CMLS · 2013Review
- Immunohistochemical analysis of IA-2 family of protein tyrosine phosphatases in rat gastrointestinal endocrine cells.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2013Article
- CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1) is a tail-anchored protein in the endoplasmic reticulum (ER) of insulinoma cells.The Journal of biological chemistry · 2012Article
- Islet autoantigens: structure, function, localization, and regulation.Cold Spring Harbor perspectives in medicine · 2012Review
- Equilibrium unfolding of the PDZ domain of β2-syntrophin.Biophysical journal · 2012Article
- Coupling of metabolic, second messenger pathways and insulin granule dynamics in pancreatic beta-cells: a computational analysis.Progress in biophysics and molecular biology · 2011Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin maintains homeostasis of glucose by promoting its uptake into cells from the blood. Hyperglycemia triggers secretion of insulin from pancreatic beta-cells. This process is mediated by secretory granule exocytosis. However, how beta-cells keep granule stores relatively constant is still unknown. ICA512 is an intrinsic granule membrane protein, whose cytosolic domain binds beta2-syntrophin, an F-actin-associated protein, and is cleaved upon granule exocytosis. The resulting cleaved cytosolic fragment, ICA512-CCF, reaches the nucleus and up-regulates the transcription of granule genes, including insulin and ICA512. Here, we show that ICA512-CCF also dimerizes with intact ICA512 on granules, thereby displacing it from beta2-syntrophin. This leads to increased granule mobility and insulin release. Based on these findings, we propose a model whereby the generation of ICA512-CCF first amplifies insulin secretion. The ensuing reduction of granule stores would then increase the probability of newly generated ICA512-CCF to reach the nucleus and enhance granule biogenesis, thus allowing beta-cells to constantly adjust production of granules to their storage size and consumption. Pharmacological modulation of these feedback loops may alleviate deficient insulin release in diabetes.
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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 OpenQuestion graph.