Coordinated Cellular Behavior Regulated by Epinephrine Neurotransmitters in the Nerveless Placozoa

Understanding how cells communicated before the evolution of nervous systems in early metazoans is key to unraveling the origins of multicellular life. We focused on Trichoplax adhaerens, one of the earliest multicellular animals, to explore this question. Through screening a small compound library targeting G protein-coupled receptors (GPCRs), we found that Trichoplax exhibits distinctive rotational movements when exposed to epinephrine. Further studies suggested that, akin to those in humans, this basal organism also utilizes adrenergic signals to regulate its negative taxis behavior, with the downstream signaling pathway being more straightforward and efficient. Mechanistically, the binding of ligands activates downstream calcium signaling, subsequently modulating ciliary redox signals. This process ultimately regulates the beating direction of cilia, governing the coordinated movement of the organism. Our findings not only highlight the enduring presence of adrenergic signaling in stress responses during evolution but also underscore the importance of early metazoan expansion of GPCR families. This amplification empowers us with the ability to sense external cues and modulate cellular communication effectively.