Cloning of the choroid plexus 5-HT_1C receptor

Abstract

In the limited time that molecular cloning techniques have been successfully applied to neurotransmitter receptors, we have learned of strong sequence homologies among one group of receptors, the G protein-coupled receptors, that unite these proteins into one structural family [1]. Members of this family include the muscarinic cholinoceptors, alpha- and beta-adrenoceptors, opsin and the Substance K receptor [1, 2]. All members of this family are single subunit proteins containing seven membrane-spanning domains with interconnecting extracellular and cytoplasmic sequences. The transmembrane domains exhibit strong sequence homologies among the family members, while the interconnecting water soluble domains are less well conserved. Recently, the 5-HT_1C receptor became the first serotonergic member of this family of cloned G-protein-coupled receptors, and so became the first 5-hydroxytryptamine (5-HT) receptor subtype to be understood at the amino acid sequence level [3, 4]. The strategy used to clone the 5-HT_1C receptor is a powerful new approach to molecular cloning, which will be broadly applicable to many receptor and ion channel proteins. The basics of this strategy will be reviewed in this chapter, along with information it has provided on the structure of the 5-HT_1C receptor.