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J Biol Chem, Vol. 274, Issue 38, 27145-27152, September 17, 1999

Up-regulation of Cell-surface 42 Neuronal Nicotinic Receptors by Lower Temperature and Expression of Chimeric Subunits

From the Wellcome Laboratory for Molecular Pharmacology, Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom

The predominant nicotinic acetylcholine receptor (nAChR) expressed in vertebrate brain is a pentamer containing 4 and 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 42 nAChR. Functional recombinant 42 nAChRs, showing high affinity binding of nicotinic radioligands (K_d = 41 ± 22 pM for [³H]epibatidine), are expressed in both stably and transiently transfected mammalian cell lines. Despite this, only very low levels of 42 nAChRs can be detected on the cell surface of transfected mammalian cells maintained at 37 °C. At 30 °C, however, cells expressing 42 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" 4 and 2 subunits, chimeric nicotinic/serotonergic subunits ("4" and "2") are expressed very efficiently on the cell surface (at 30 °C or 37 °C), either as hetero-oligomeric complexes (e.g. 4+2 or 4+2) or when expressed alone. Compared with 42 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.

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