Chimeric Gαq 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 subtypes. 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 is incapable of activating the pertussis toxin-insensitive G(16). Here we used three well-characterized Ca, chimeras to explore the coupling specificity of the melatonin receptors. The qi5, qo5, and qz5 chimeras can link numerous G(i)-coupled receptors to the stimulation of phosphoinositide-specific phospholipase C. Both mtl and MT2 receptors interacted productively with the G alpha (q) chimeras, while the long form of Melic was totally ineffective. Among the Ga, chimeras, qo5 was less efficiently coupled to the melatonin receptors. Such differential coupling is best explained by structural differences between the melatonin receptors as well as among the G alpha (q) chimeras. Since the long form of Melic receptor possesses an exceptionally large C-terminal tail, we tested the ability of four melatonin receptor C-terminal tail chimeras (Chi 1-4) to interact with the Ca, chimeras. The presence of the large C-terminal tail of Melic in Chi 1 and Chi 3 markedly hindered 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 chimeras (Chi 2 and Chi 4) that were capable of activating the Ga, chimeras. These findings suggest the involvement of C-terminal regions of melatonin receptors in the recognition of G proteins.