Very recently, the Tosini lab published a paper in Science Signaling! Many congratulations! The paper investigated the impact of melatonin receptor cascades on eye function at physiological and molecular levels. Using a combination of transgenic mice and mutant cell lines coupled with electrophysiological recordings, pharmacology, histology, and wet lab work, it was found that the MT1 and MT2 receptors–of which melatonin binds to– form a heterodimer in the photoreceptors and this heterodimer mediates the action of melatonin on these cells.
In the first series of experiments, electrophysiological output from the retina was measured. The extent of retina activity was quantified by measuring two discrete, waveforms known as a and b waves. In mice lacking the MT2 receptor, the difference in electrophysiological output between the mid-night, when mice are active, and mid-day, when mice are typically asleep, was gone. The usual time-dependent difference could also not be restored by melatonin injections. This is indicates the importance of the MT2 receptor. A similar result was also found in mice lacking the MT1 receptor.
Next, an examination of structure and location of MT1/MT2 receptors was undertaken. It was found that MT1/MT2 receptors heteromize–expressed together–and are found primarily in the photoreceptors. What’s cool about this experiment is that an antibody for MT2 is not commercially available. To get around this, a fluorescent tag for MT receptors was inserted in the mice so that a typical immunofluorescent stain could be done.
In an additional series of experiments, the researchers also examined the impact of a mutant form of the MT2 receptor on formation of the MT1/MT2 heterodimer and photoreceptors function in the presence an absence of melatonin. There again, eye function was disrupted. Finally, the researchers investigated the intracellular signaling cascades that are activated by the MT1/MT2 heterodimer in the photoreceptors.
In all, the study strengthens the argument that melatonin has a significant impact on photorecepto function. In the world of biomedical research, the melatonin cascade may be an ideal target for the treatment of vision problems.
Baba K, Benleulmi-Chaachoua A, Journé AS, Kamal M, Guillaume JL, Dussaud S, Gbahou F, Yettou K, Liu C, Contreras-Alcantara S, Jockers R, & Tosini G (2013). Heteromeric MT1/MT2 Melatonin Receptors Modulate Photoreceptor Function. Science signaling, 6 (296) PMID: 24106342