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Photolysis of cell-permeant caged inositol pyrophosphates controls oscillations of cytosolic calcium in a β-cell line

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Abstract

Among many cellular functions, inositol pyrophosphates (PP-InsPs) are metabolic messengers involved in the regulation of glucose uptake, insulin sensitivity, and weight gain. However, their mechanisms of action are still poorly understood. So far, the influence of PP-InsPs on cellular metabolism has been studied by overexpression or knockout/inhibition of relevant metabolizing kinases (IP6Ks, PPIP5Ks). These approaches are, inter alia, limited by time-resolution and potential compensation mechanisms. Here, we describe the synthesis of cell-permeant caged PP-InsPs as tools to rapidly modulate intracellular levels of defined isomers of PP-InsPs in a genetically non-perturbed cellular environment. We show that caged prometabolites readily enter live cells where they are enzymatically converted into still inactive, metabolically stable, photocaged PP-InsPs. Upon light-triggered release of 5-PP-InsP5, the major cellular inositol pyrophosphate, oscillations of intracellular Ca2+ levels in MIN6 cells were transiently reduced to spontaneously recover again. In contrast, uncaging of 1-PP-InsP5, a minor cellular isomer, was without effect. These results provide evidence that PP-InsPs play an active role in regulating [Ca2+]i oscillations, a key element in triggering exocytosis and secretion in β-cells.

Graphical abstract: Photolysis of cell-permeant caged inositol pyrophosphates controls oscillations of cytosolic calcium in a β-cell line

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Publication details

The article was received on 05 Aug 2018, accepted on 09 Jan 2019 and first published on 10 Jan 2019


Article type: Edge Article
DOI: 10.1039/C8SC03479F
Citation: Chem. Sci., 2019, Advance Article
  • Open access: Creative Commons BY license
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    Photolysis of cell-permeant caged inositol pyrophosphates controls oscillations of cytosolic calcium in a β-cell line

    S. Hauke, A. K. Dutta, V. B. Eisenbeis, D. Bezold, T. Bittner, C. Wittwer, D. Thakor, I. Pavlovic, C. Schultz and H. J. Jessen, Chem. Sci., 2019, Advance Article , DOI: 10.1039/C8SC03479F

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