ArticleJournal of cell science2016
Optogenetic activation reveals distinct roles of PIP3 and Akt in adipocyte insulin action.
Article in Journal of cell science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 58 citations in OpenAlex.
- Signaling Connectomics: A Brain-wide Framework for Intercellular Communication.Experimental neurobiology · 2026Article
- Oncogenic Alterations in PI3K Signaling Emulated Optogenetically Recapitulate Some Phenotypic Changes in Mammary Epithelia.ACS synthetic biology · 2026Article
- POT, an optogenetics-based endogenous protein degradation system.Communications biology · 2025Article
- Optogenetic control of Protein Kinase C-epsilon activity reveals its intrinsic signaling properties with spatiotemporal resolution.bioRxiv : the preprint server for biology · 2025Article
- Research progress on the pathogenesis, clinical impact, and traditional Chinese medicine treatment of polycystic ovary syndrome complicated by insulin resistance.Frontiers in pharmacology · 2025Review
- Optogenetic therapeutic strategies for diabetes mellitus.Journal of diabetes · 2024Review
- Optogenetic control of mitochondrial aggregation and function.Frontiers in bioengineering and biotechnology · 2024Article
- An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells.Nature communications · 2023Article
- Regulation of EGF-stimulated activation of the PI-3K/AKT pathway by exocyst-mediated exocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- GLUT4 On the move.The Biochemical journal · 2022Article
- Ubiquitin-like processing of TUG proteins as a mechanism to regulate glucose uptake and energy metabolism in fat and muscle.Frontiers in endocrinology · 2022Review
- CaJournal of cellular physiology · 2021Article
- Optogenetic Approaches for the Spatiotemporal Control of Signal Transduction Pathways.International journal of molecular sciences · 2021Review
- Insulin-stimulated endoproteolytic TUG cleavage links energy expenditure with glucose uptake.Nature metabolism · 2021Article
- Optogenetics: The Art of Illuminating Complex Signaling Pathways.Physiology (Bethesda, Md.) · 2021Review
- Light control of RTK activity: from technology development to translational research.Chemical science · 2020Review
- Optogenetic Techniques for Manipulating and Sensing G Protein-Coupled Receptor Signaling.Methods in molecular biology (Clifton, N.J.) · 2020Review
- GLUT4 Storage Vesicles: Specialized Organelles for Regulated Trafficking.The Yale journal of biology and medicine · 2019Review
- A high-throughput chemical-genetics screen in murine adipocytes identifies insulin-regulatory pathways.The Journal of biological chemistry · 2019Article
- Blue-Light Receptors for Optogenetics.Chemical reviews · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Glucose transporter 4 (GLUT4; also known as SLC2A4) resides on intracellular vesicles in muscle and adipose cells, and translocates to the plasma membrane in response to insulin. The phosphoinositide 3-kinase (PI3K)-Akt signaling pathway plays a major role in GLUT4 translocation; however, a challenge has been to unravel the potentially distinct contributions of PI3K and Akt (of which there are three isoforms, Akt1-Akt3) to overall insulin action. Here, we describe new optogenetic tools based on CRY2 and the N-terminus of CIB1 (CIBN). We used these 'Opto' modules to activate PI3K and Akt selectively in time and space in 3T3-L1 adipocytes. We validated these tools using biochemical assays and performed live-cell kinetic analyses of IRAP-pHluorin translocation (IRAP is also known as LNPEP and acts as a surrogate marker for GLUT4 here). Strikingly, Opto-PIP3 largely mimicked the maximal effects of insulin stimulation, whereas Opto-Akt only partially triggered translocation. Conversely, drug-mediated inhibition of Akt only partially dampened the translocation response of Opto-PIP3 In spatial optogenetic studies, focal targeting of Akt to a region of the cell marked the sites where IRAP-pHluorin vesicles fused, supporting the idea that local Akt-mediated signaling regulates exocytosis. Taken together, these results indicate that PI3K and Akt play distinct roles, and that PI3K stimulates Akt-independent pathways that are important for GLUT4 translocation.
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Registered trials
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.