Functional evolution of Thyrotropin-releasing hormone neuropeptides: insights from an echinoderm

Feeding behavior is regulated by a rich network of endogenous neuropeptides. In chordates, this role is suggested to be under the control of diverse factors including the Thyrotropin-releasing hormone (TRH). It is unclear, however, whether this regulatory activity of TRH is functionally conserved in non-chordate metazoans, and to what extent this process is underpinned by interactions of TRH with other neuropeptides such as Cholecystokinin (CCK, known as a satiety signal). Here, we investigated the function and pathway of the TRH signaling system in the echinoderm Apostichopus japonicus. Combining bioinformatic analyses and ligand binding assay, we identified a functional receptor (AjTRHR) of TRH peptides, activating the signaling via MAPK/ERK1/2 pathways. Next, experimental TRH administration showed a significant feeding activity decrease and the up-regulation of CCK. Further RNA inference (RNAi) experiment confirmed that CCK and TRH are both involved in satiety signals mediating feeding inhibition. Evolutionary analysis of TRH-type peptides revealed that the short-isoform TRH is more conserved compared to the long-isoform, probably driven by strong selection acting on the functional redundancy. These novel findings provide evidence of a TRH system in a non-chordate deuterostome, expanding our understanding of the peptidergic signaling-mediate feeding regulation mechanism in marine invertebrates.