Existence and functions of a kisspeptin neuropeptide signaling system in a non-chordate deuterostome species.

Abstract

The kisspeptin system is a central modulator of the hypothalamic-pituitary-gonadal axis in vertebrates. Its existence outside the vertebrate lineage remains largely unknown. Here, we report the identification and characterization of the kisspeptin system in the sea cucumber <i>Apostichopus japonicus.</i> The gene encoding the kisspeptin precursor generates two mature neuropeptides, AjKiss1a and AjKiss1b. The receptors for these neuropeptides, AjKissR1 and AjKissR2, are strongly activated by synthetic <i>A. japonicus</i> and vertebrate kisspeptins, triggering a rapid intracellular mobilization of Ca²⁺, followed by receptor internalization. AjKissR1 and AjKissR2 share similar intracellular signaling pathways via G_αq/PLC/PKC/MAPK cascade, when activated by C-terminal decapeptide. The <i>A. japonicus</i> kisspeptin system functions in multiple tissues that are closely related to seasonal reproduction and metabolism. Overall, our findings uncover for the first time the existence and function of the kisspeptin system in a non-chordate species and provide new evidence to support the ancient origin of intracellular signaling and physiological functions that are mediated by this molecular system.