Deconvolution of complex G protein-coupled receptor signaling in live cells using dynamic mass redistribution measurements

Schroder, R. et al. (2010) Deconvolution of complex G protein-coupled receptor signaling in live cells using dynamic mass redistribution measurements. Nature Biotechnology, 28(9), pp. 943-949. (doi: 10.1038/nbt.1671)

Abstract

Label-free biosensor technology based on dynamic mass redistribution (DMR) of cellular constituents promises to translate GPCR signaling into complex optical 'fingerprints' in real time in living cells. Here we present a strategy to map cellular mechanisms that define label-free responses, and we compare DMR technology with traditional second-messenger assays that are currently the state of the art in GPCR drug discovery. The holistic nature of DMR measurements enabled us to (i) probe GPCR functionality along all four G-protein signaling pathways, something presently beyond reach of most other assay platforms; (ii) dissect complex GPCR signaling patterns even in primary human cells with unprecedented accuracy; (iii) define heterotrimeric G proteins as triggers for the complex optical fingerprints; and (iv) disclose previously undetected features of GPCR behavior. Our results suggest that DMR technology will have a substantial impact on systems biology and systems pharmacology as well as for the discovery of drugs with novel mechanisms.

• Item Type: Articles
• Additional Information: The final, publisher-edited version of this article is available from Nature.com. <BR/> <BR/> Original title: Deconvolution of complex g protein-coupled receptor signaling in live cells: taking advantage of the resolving power of dynamic mass redistribution technology
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Milligan, Professor Graeme and Smith, Dr Nicola
• Authors: Schroder, R., Janssen, N., Schmidt, J., Kebig, A., Merten, N., Hennen, S., Muller, A., Blattermann, S., Mohr-Andra, M., Zahn, S., Wenzel, J., Smith, N.J., Gomeza, J., Drewke, C., Milligan, G., Mohr, K., and Kostenis, E.
• Subjects: Q Science > QH Natural history > QH345 Biochemistry
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Nature Biotechnology
• Publisher: Nature Publishing Group
• ISSN: 1087-0156
• ISSN (Online): 1546-1696
• Published Online: 15 August 2010
• Copyright Holders: Copyright © 2010 Nature Publishing Group
• First Published: First published in Nature Biotechnology 28(9):943-494
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher