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Really happy to see this story published as it goes back to my first steps in neuroscience as an undergraduate student. Big thanks to everyone involved, especially my co-author @irinamarcovich and supervisors @AElgoyhen and Marcela Lipovsek https://www.frontiersin.org/article/10.3389/fnmol.2021.639720
In the mammalian lineage, the cochlear nicotinic receptor α9α10 has accumulated several changes at the protein level, but how this may relate to the evolutionary history of the hearing organ is still an open question.
We found that choline, the metabolite of acetylcholine degradation at the synaptic cleft, shows reduced efficacy in mammalian rat α9α10 receptors compared to non-mammalian chicken receptors. This might have contributed to shape cholinergic synaptic responses.
Analysis of hybrid rat-chicken receptors and molecular docking studies performed by @CorradiJere suggested that the α10 subunit bears the responsibility for this difference.
We mutated the α10 subunit binding site to find out that it determined choline efficacy in mammalian α9α10 receptors whereas responses to ACh remained unaltered.
Strong positive selection pressure for the loss of the agonistic function of choline may have been the driver for the accumulation of coding sequence changes within mammalian α10 subunits to shape the fine-tuned high-frequency efferent olivocochlear activity.
Thank you for reading till the end and many thanks to all the team that helped to bring this project to completion!!! @irinamarcovich @AElgoyhen @CorradiJere @bio_fosi @ilcarbo @AudicionLab
