Chimeric Gα_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 mt1, MT2, and Me11c subtypes. The Me11c is further divided into one long and two short isoforms. A recent study has shown that, unlike mt1 and MT2, the long form of Me11c is incapable of activating the pertussis toxin-insensitive G₁₆. Here we used three well-characterized Gα_q 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 mt1 and MT2 receptors interacted productively with the Gα_q chimeras, while the long form of Me11c was totally ineffective. Among the Gα_q 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 Gα_q chimeras. Since the long form of Me11c 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 Gα_q chimeras. The presence of the large C-terminal tail of Me11c in Chi 1 and Chi 3 markedly hindered their coupling to the Gα_q chimeras. On the other hand, the attachment of either the mt1 or MT2 C-terminal tail to a Me11c backbone produced chimeras (Chi 2 and Chi 4) that were capable of activating the Gα_q chimeras. These findings suggest the involvement of C-terminal regions of melatonin receptors in the recognition of G proteins.