Chimeric G alpha(q) subunits can distinguish the long form of the Xenopus Me11c melatonin receptor from the mammalian mt1 and MT2 melatonin receptors

The family of melatonin receptors is composed of the mtl, MT2, and Melic su btypes. The Melic is further divided into one long and two short isoforms. A recent study has shown that, unlike mtl and MT2, the long form of Melic i s incapable of activating the pertussis toxin-insensitive G(16). Here we us ed three well-characterized Ca, chimeras to explore the coupling specificit y of the melatonin receptors. The qi5, qo5, and qz5 chimeras can link numer ous G(i)-coupled receptors to the stimulation of phosphoinositide-specific phospholipase C. Both mtl and MT2 receptors interacted productively with th e G alpha (q) chimeras, while the long form of Melic was totally ineffectiv e. Among the Ga, chimeras, qo5 was less efficiently coupled to the melatoni n receptors. Such differential coupling is best explained by structural dif ferences between the melatonin receptors as well as among the G alpha (q) c himeras. Since the long form of Melic receptor possesses an exceptionally l arge C-terminal tail, we tested the ability of four melatonin receptor C-te rminal tail chimeras (Chi 1-4) to interact with the Ca, chimeras. The prese nce of the large C-terminal tail of Melic in Chi 1 and Chi 3 markedly hinde red their coupling to the Gee, chimeras. On the other hand, the attachment of either the mtl or MT2 C-terminal tail to a Melic backbone produced chime ras (Chi 2 and Chi 4) that were capable of activating the Ga, chimeras. The se findings suggest the involvement of C-terminal regions of melatonin rece ptors in the recognition of G proteins.