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Up-regulation of cell-surface alpha 4 beta 2 neuronal nicotinic receptors by lower temperature and expression of chimeric subunits

Cooper, ST; Harkness, PC; Baker, ER; Millar, NS; (1999) Up-regulation of cell-surface alpha 4 beta 2 neuronal nicotinic receptors by lower temperature and expression of chimeric subunits. J BIOL CHEM , 274 (38) 27145 - 27152. Gold open access

Abstract

The predominant nicotinic acetylcholine receptor (nAChR) expressed in vertebrate brain is a pentamer containing alpha 4 and beta 2 subunits, In this study we have examined how temperature and the expression of subunit chimeras can influence the efficiency of cell-surface expression of the rat alpha 4 beta 2 nAChR, Functional recombinant alpha 4 beta 2 nAChRs, showing high affinity binding of nicotinic radioligands (K-d = 41 +/- 22 pM for [H-3]epibatidine), are expressed in both stably and transiently transfected mammalian cell lines, Despite this, only very low levels of alpha 4 beta 2 nAChRs can be detected on the cell surface of transfected mammalian cells maintained at 37 degrees C. At 30 degrees C, however, cells expressing alpha 4 beta 2 nAChRs show a 12-fold increase in radioligand binding (with no change in affinity), and a 5-fold up-regulation in cell-surface receptors with no increase in total subunit protein. In contrast to "wild-type" alpha 4 and beta 2 subunits, chimeric nicotinic/serotonergic subunits ("alpha 4 chi" and "beta 2 chi") are expressed very efficiently on the cell surface (at 30 degrees C or 37 degrees C), either as hetero-oligomeric complexes (e.g. alpha 4 chi+beta 2 or alpha 4 chi+beta 2 chi) or when expressed alone. Compared with alpha 4 beta 2 nAChRs, expression of complexes containing: chimeric subunits typically results in up to 20-fold increase in nicotinic radioligand binding sites (with no change in affinity) and a similar increase in cell-surface receptor, despite a similar level of total chimeric and wild-type protein.

Type: Article
Title: Up-regulation of cell-surface alpha 4 beta 2 neuronal nicotinic receptors by lower temperature and expression of chimeric subunits
Open access status: An open access publication
Publisher version: http://www.jbc.org/content/early/recent/0
Keywords: ACETYLCHOLINE-RECEPTOR, ION-CHANNEL, RAT-BRAIN, FUNCTIONAL EXPRESSION, SENSITIVE EXPRESSION, TRANSFECTED CELLS, MOUSE FIBROBLASTS, XENOPUS OOCYTES, BETA-SUBUNIT, MUSCLE-CELLS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/186535
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