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| Item Type: | Article |
|---|---|
| Title: | Receptor-associated independent cAMP nanodomains mediate spatiotemporal specificity of GPCR signaling |
| Creators Name: | Anton, S.E., Kayser, C., Maiellaro, I., Nemec, K., Möller, J., Koschinski, A., Zaccolo, M., Annibale, P., Falcke, M., Lohse, M.J. and Bock, A. |
| Abstract: | G protein-coupled receptors (GPCRs) relay extracellular stimuli into specific cellular functions. Cells express many different GPCRs, but all these GPCRs signal to only a few second messengers such as cAMP. It is largely unknown how cells distinguish between signals triggered by different GPCRs to orchestrate their complex functions. Here, we demonstrate that individual GPCRs signal via receptor-associated independent cAMP nanodomains (RAINs) that constitute self-sufficient, independent cell signaling units. Low concentrations of glucagon-like peptide 1 (GLP-1) and isoproterenol exclusively generate highly localized cAMP pools around GLP-1- and β(2)-adrenergic receptors, respectively, which are protected from cAMP originating from other receptors and cell compartments. Mapping local cAMP concentrations with engineered GPCRnanorulers reveals gradients over only tens of nanometers that define the size of individual RAINs. The coexistence of many such RAINs allows a single cell to operate thousands of independent cellular signals simultaneously, rather than function as a simple "on/off" switch. |
| Keywords: | G Protein-Coupled Receptors, cAMP, Compartmentation, Cell Signaling, FRET, Biosensors, Nanodomains, Spatiotemporal Signaling, Diffusion, GLP-1 |
| Source: | Cell |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Volume: | 185 |
| Number: | 7 |
| Page Range: | 1130-1142.e11 |
| Date: | 31 March 2022 |
| Additional Information: | Copyright © 2022 Elsevier Inc. This manuscript version is made available under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ or send a letter to Creative Commons, PO Box 1866, Mountain View, CA 94042, USA. |
| Official Publication: | https://doi.org/10.1016/j.cell.2022.02.011 |
| PubMed: | View item in PubMed |
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