Hormone-Induced Calcium Oscillations Depend on Cross-Coupling with Inositol 1,4,5-Trisphosphate Oscillations
| Autor: | Suresh K. Joseph, Andrew P. Thomas, Jane Johnston, Paul Burnett, Lawrence D. Gaspers, Thomas Höfer, Walson Metzger, Paula J. Bartlett, Antonio Z. Politi |
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| Jazyk: | angličtina |
| Předmět: |
inorganic chemicals
endocrine system Vasopressins education Green Fluorescent Proteins chemistry.chemical_element Inositol 1 4 5-Trisphosphate Calcium Ligands Models Biological Article General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Chlorocebus aethiops Animals Inositol 1 4 5-Trisphosphate Receptors Computer Simulation Inositol Calcium Signaling Receptor lcsh:QH301-705.5 Calcium signaling Protein Structure Tertiary Rats Coupling (electronics) carbohydrates (lipids) lcsh:Biology (General) chemistry Cytosolic ca COS Cells Hepatocytes Biophysics Steady state (chemistry) Hormone |
| Zdroj: | Cell reports Cell Reports, Vol 9, Iss 4, Pp 1209-1218 (2014) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2014.10.033 |
| Popis: | SUMMARY Receptor-mediated oscillations in cytosolic Ca2+ concentration ([Ca2+]i) could originate either directly from an autonomous Ca2+ feedback oscillator at the inositol 1,4,5-trisphosphate (IP3) receptor or as a secondary consequence of IP3 oscillations driven by Ca2+ feedback on IP3 metabolism. It is challenging to discriminate these alternatives, because IP3 fluctuations could drive Ca2+ oscillations or could just be a secondary response to the [Ca2+]i spikes. To investigate this problem, we constructed a recombinant IP3 buffer using type-I IP3 receptor ligand-binding domain fused to GFP (GFP-LBD), which buffers IP3 in the physiological range. This IP3 buffer slows hormone-induced [IP3] dynamics without changing steady-state [IP3]. GFP-LBD perturbed [Ca2+]i oscillations in a dose-dependent manner: it decreased both the rate of [Ca2+]i rise and the speed of Ca2+ wave propagation and, at high levels, abolished [Ca2+]i oscillations completely. These data, together with computational modeling, demonstrate that IP3 dynamics play a fundamental role in generating [Ca2+]i oscillations and waves. Graphical Abstract In Brief Gaspers et al. use a genetically encoded IP3 buffer to suppress IP3 dynamics during hormonal stimulation. Using this approach, they find that positive feedback of Ca2+ on IP3 formation is an essential component, generating long-period, baseline-separated Ca2+ oscillations and intracellular Ca2+ waves. |
| Databáze: | OpenAIRE |
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