Gs protein-coupled serotonin receptors: receptor isoforms and functional differences

Three distinct mammalian Gs coupled serotonin receptor genes have been identified, 5-HT4, 5-ht6, and 5-HT7, which produce at least seven different functional receptors through alternative splicing. One of the chief questions facing workers in this area mirrors that confronting the serotonin receptor field as a whole: why so many subtypes? The answer to this question is made more elusive at present by two further considerations. First, there may well be additional Gs coupled receptor subtypes yet to be described. Secondly, although the various isoforms of 5-HT4 and 5-HT7 have been shown to be functional in in vitro assays, it remains to be shown that all isoforms have biological significance. This paper will summarize some of the differences at the molecular and cellular level that are becoming apparent among the 5-HT4, 5-ht6 and 5-HT7 receptor subtypes and their various isoforms. As an example, it will focus on the 5-HT7 system, and describe recent developments in ascribing particular functions to differences due to alternative splicing.