Chimeric Gαq subunits can distinguish the long form of the Xenopus Mel1c melatonin receptor from the mammalian mt1 and MT2 melatonin receptors

The family of melatonin receptors is composed of the mtl, MT2, and Mellc subtypes. The Mellc is further divided into one long and two short isoforms. A recent study has shown that, unlike mtl and MT2, the long form of Mellc is incapable of activating the pertussis toxin-insensitive G 16 . 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 mtl and MT2 receptors interacted productively with the Gα q chimeras, while the long form of Mellc 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 Mellc 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 Mellc in Chi I and Chi 3 markedly hindered their coupling to the Gα q chimeras. On the other hand, the attachment of either the mtl or MT2 C-terminal tail to a Mellc 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.