Photolysis of Caged Inositol Pyrophosphate InsP8 Directly Modulates Intracellular Ca2+ Oscillations and Controls C2AB Domain Localization
| العنوان: | Photolysis of Caged Inositol Pyrophosphate InsP8 Directly Modulates Intracellular Ca2+ Oscillations and Controls C2AB Domain Localization |
|---|---|
| المؤلفون: | Stephan Mundinger, Christopher Wittwer, Sebastian Hauke, Carsten Schultz, Tamara Bittner, Henning J. Jessen, Tobias Dürr, Daniel Wohlwend, Amit K. Dutta, Dominik Bezold, Thorsten Friedrich |
| المصدر: | Journal of the American Chemical Society. 142:10606-10611 |
| بيانات النشر: | American Chemical Society (ACS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cell signaling, Chemistry, General Chemistry, Biochemistry, Pyrophosphate, Catalysis, Calcium in biology, chemistry.chemical_compound, Cytosol, Membrane docking, Colloid and Surface Chemistry, Biophysics, Inositol, Intracellular, Calcium signaling |
| الوصف: | Inositol pyrophosphates constitute a family of hyperphosphorylated signaling molecules involved in the regulation of glucose uptake and insulin sensitivity. While our understanding of the biological roles of inositol heptaphosphates (PP-InsP5) has greatly improved, the functions of the inositol octaphosphates ((PP)2-InsP4) have remained unclear. Here we present the synthesis of two enantiomeric cell-permeant and photocaged (PP)2-InsP4 derivatives and apply them to study the functions in living β-cells. Photorelease of the naturally occurring isomer 1,5-(PP)2-InsP4 led to an immediate and concentration-dependent reduction of intracellular calcium oscillations, while other caged inositol pyrophosphates (3,5-(PP)2-InsP4, 5-PP-InsP5, 1-PP-InsP5, 3-PP-InsP5) showed no immediate effect. Furthermore, uncaging of 1,5-(PP)2-InsP4 but not 3,5-(PP)2-InsP4 induced translocation of the C2AB domain of granuphilin from the plasma membrane to the cytosol. Granuphilin is involved in membrane docking of secretory vesicles. This suggests that 1,5-(PP)2-InsP4 impacts β-cell activity by regulating granule localization and/or priming and calcium signaling in concert. |
| تدمد: | 1520-5126 0002-7863 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::08854ae7b11fcdba043623b90b0931bcTest https://doi.org/10.1021/jacs.0c01697Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........08854ae7b11fcdba043623b90b0931bc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15205126 00027863 |
|---|