ArticleThe Journal of cell biology2019
The PI(4)P phosphatase Sac2 controls insulin granule docking and release.
Article in The Journal of cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Spatial organization of phosphoinositide signaling.FEBS letters · 2026Review
- Phosphatidylinositol-4-phosphate signaling regulates dense granule biogenesis and maturation in Toxoplasma gondii.PLoS pathogens · 2026Article
- Restoration of PITPNA in Type 2 diabetic human islets reverses pancreatic beta-cell dysfunction.Nature communications · 2023Article
- Rab26 restricts insulin secretion via sequestering Synaptotagmin-1.PLoS biology · 2023Article
- Parkinson disease-associated Leucine-rich repeat kinase regulates UNC-104-dependent axonal transport of Arl8-positive vesicles iniScience · 2022Article
- PI4P/PS countertransport by ORP10 at ER-endosome membrane contact sites regulates endosome fission.The Journal of cell biology · 2022Article
- Insulin granule biogenesis and exocytosis.Cellular and molecular life sciences : CMLS · 2021Review
- Functions of Oxysterol-Binding Proteins at Membrane Contact Sites and Their Control by Phosphoinositide Metabolism.Frontiers in cell and developmental biology · 2021Review
- The type 2 diabetes gene product STARD10 is a phosphoinositide-binding protein that controls insulin secretory granule biogenesis.Molecular metabolism · 2020Article
- Absence of Sac2/INPP5F enhances the phenotype of a Parkinson's disease mutation of synaptojanin 1.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Membrane trafficking in health and disease.Disease models & mechanisms · 2020Review
- Membrane Heterogeneity Controls Cellular Endocytic Trafficking.Frontiers in cell and developmental biology · 2020Review
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin granule biogenesis involves transport to, and stable docking at, the plasma membrane before priming and fusion. Defects in this pathway result in impaired insulin secretion and are a hallmark of type 2 diabetes. We now show that the phosphatidylinositol 4-phosphate phosphatase Sac2 localizes to insulin granules in a substrate-dependent manner and that loss of Sac2 results in impaired insulin secretion. Sac2 operates upstream of granule docking, since loss of Sac2 prevented granule tethering to the plasma membrane and resulted in both reduced granule density and number of exocytic events. Sac2 levels correlated positively with the number of docked granules and exocytic events in clonal β cells and with insulin secretion in human pancreatic islets, and Sac2 expression was reduced in islets from type 2 diabetic subjects. Taken together, we identified a phosphoinositide switch on the surface on insulin granules that is required for stable granule docking at the plasma membrane and impaired in human type 2 diabetes.
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