ArticleMolecular metabolism2020
The type 2 diabetes gene product STARD10 is a phosphoinositide-binding protein that controls insulin secretory granule biogenesis.
Article in Molecular metabolism, 2020. 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, 31 citations in OpenAlex.
- STARD10 promotes progression of HER2+ breast cancer and intracellular lipid metabolism via the cAMP/PKA/CREB1 signaling axis.Cancer biology & therapy · 2026Article
- A cryptic START domain regulates deeply conserved transcription factors.The Plant cell · 2026Article
- Differential lipid selectivity of StARD phospholipid transporters revealed by native MS.Nature communications · 2026Article
- Single-Cell Analysis Reveals STARD10 as a Fatty Acid Metabolism Regulator of Breast Cancer Progression via the PI3K/Akt Pathway.International journal of molecular sciences · 2026Article
- Proteomic analyses of human islets reveal potential markers of β cell dysfunction during prediabetes.JCI insight · 2026Article
- STARD10 regulates human pancreatic β cell differentiation and triglyceride metabolism.Stem cell reports · 2026Article
- DNA Methylation Variation in Blood Cells may Impact Platelet Function.TH open : companion journal to thrombosis and haemostasis · 2026Article
- Mechanistic insights into cargo sorting and export from the Golgi apparatus.Nature reviews. Molecular cell biology · 2025Review
- Genetic variations and functions of KLF14 in gene expression and metabolic disease development.Journal of applied genetics · 2025Review
- Antioxidant, Antimicrobial, Anticancer, and Molecular Docking Insights into Pancratium maritimum Seeds and Flowers: A Phytochemical Approach.ChemistryOpen · 2025Article
- START domains generate paralog-specific regulons from a single network architecture.Nature communications · 2024Article
- A Rab6 to Rab11 transition is required for dense-core granule and exosome biogenesis in Drosophila secondary cells.PLoS genetics · 2023Article
- Nuclear Phosphoinositides as Key Determinants of Nuclear Functions.Biomolecules · 2023Review
- 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
- Loci for insulin processing and secretion provide insight into type 2 diabetes risk.American journal of human genetics · 2023Article
- Biochemical Activation and Regulatory Functions of Trans-Regulatory KLF14 and Its Association with Genetic Polymorphisms.Metabolites · 2023Review
- Cholesterol Redistribution in Pancreatic β-Cells: A Flexible Path to Regulate Insulin Secretion.Biomolecules · 2023Review
- Genetic evidence for a causal relationship between type 2 diabetes and peripheral artery disease in both Europeans and East Asians.BMC medicine · 2022Article
- Inflammatory stress signaling via NF-eLife · 2022Article
- Mitofusins Mfn1 and Mfn2 Are Required to Preserve Glucose- but Not Incretin-Stimulated β-Cell Connectivity and Insulin Secretion.Diabetes · 2022Article
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Authors and funding
31 authors at 13 institutions in 6 countries.
Funding
Abstract
objectiveRisk alleles for type 2 diabetes at the STARD10 locus are associated with lowered STARD10 expression in the β-cell, impaired glucose-induced insulin secretion, and decreased circulating proinsulin:insulin ratios. Although likely to serve as a mediator of intracellular lipid transfer, the identity of the transported lipids and thus the pathways through which STARD10 regulates β-cell function are not understood. The aim of this study was to identify the lipids transported and affected by STARD10 in the β-cell and the role of the protein in controlling proinsulin processing and insulin granule biogenesis and maturation.
methodsWe used isolated islets from mice deleted selectively in the β-cell for Stard10 (βStard10KO) and performed electron microscopy, pulse-chase, RNA sequencing, and lipidomic analyses. Proteomic analysis of STARD10 binding partners was executed in the INS1 (832/13) cell line. X-ray crystallography followed by molecular docking and lipid overlay assay was performed on purified STARD10 protein.
resultsβStard10KO islets had a sharply altered dense core granule appearance, with a dramatic increase in the number of "rod-like" dense cores. Correspondingly, basal secretion of proinsulin was increased versus wild-type islets. The solution of the crystal structure of STARD10 to 2.3 Å resolution revealed a binding pocket capable of accommodating polyphosphoinositides, and STARD10 was shown to bind to inositides phosphorylated at the 3' position. Lipidomic analysis of βStard10KO islets demonstrated changes in phosphatidylinositol levels, and the inositol lipid kinase PIP4K2C was identified as a STARD10 binding partner. Also consistent with roles for STARD10 in phosphoinositide signalling, the phosphoinositide-binding proteins Pirt and Synaptotagmin 1 were amongst the differentially expressed genes in βStard10KO islets.
conclusionOur data indicate that STARD10 binds to, and may transport, phosphatidylinositides, influencing membrane lipid composition, insulin granule biosynthesis, and insulin processing.
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