Patowary, S., Alvarez-Curto, E. , Xu, T.-R., Holz, J.D., Oliver, J.A., Milligan, G. and Raicu, V. (2013) The muscarinic M3acetylcholine receptor exists as two differently sized complexes at the plasma membrane. Biochemical Journal, 452(2), pp. 303-312. (doi: 10.1042/BJ20121902) (PMID:23521066)
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Publisher's URL: http://dx.doi.org/10.1042/BJ20121902
Abstract
The literature on GPCR (G-protein-coupled receptor) homo-oligomerization encompasses conflicting views that range from interpretations that GPCRs must be monomeric, through comparatively newer proposals that they exist as dimers or higher-order oligomers, to suggestions that such quaternary structures are rather ephemeral or merely accidental and may serve no functional purpose. In the present study we use a novel method of FRET (Förster resonance energy transfer) spectrometry and controlled expression of energy donor-tagged species to show that M3Rs (muscarinic M3 acetylcholine receptors) at the plasma membrane exist as stable dimeric complexes, a large fraction of which interact dynamically to form tetramers without the presence of trimers, pentamers, hexamers etc. That M3R dimeric units interact dynamically was also supported by co-immunoprecipitation of receptors synthesized at distinct times. On the basis of all these findings, we propose a conceptual framework that may reconcile the conflicting views on the quaternary structure of GPCRs.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Xu, Professor Tianrui and Alvarez-Curto, Dr Elisa and Milligan, Professor Graeme |
Authors: | Patowary, S., Alvarez-Curto, E., Xu, T.-R., Holz, J.D., Oliver, J.A., Milligan, G., and Raicu, V. |
College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
Journal Name: | Biochemical Journal |
Publisher: | Portland Press Ltd. |
ISSN: | 0264-6021 |
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