Promiscuous melanocortin receptors in hagfish indicate that receptor function preceded peptide specialization

Area of Science:

• Endocrinology
• Evolutionary Biology
• Genomics

Background:

• Hagfishes represent an early vertebrate lineage (Agnatha) with poorly understood endocrine systems.
• Melanocortin receptors (Mcrs) and their accessory protein (Mrap) are crucial in vertebrate signaling but their function in hagfish is unknown.

Purpose of the Study:

• To molecularly and functionally characterize Mcrs and Mrap in hagfishes.
• To investigate the evolutionary origins of the vertebrate melanocortin system.

Main Methods:

• Genomic and transcriptomic analysis of hagfish species (Eptatretus burgeri, Eptatretus stoutii, Myxine glutinosa).
• Expression of hagfish Mcrs and Mrap in mammalian cells to assess receptor function and ligand response.
• Gene expression analysis in hagfish tissues.

Main Results:

• Identified two hagfish Mcrs (Mcar, Mcbr) and one Mrap.
• Both receptors responded to ACTH(1-24) and α-MSH; Mrap modulated Mcbr activity.
• Mcbr and Mrap were highly expressed in the slime gland, while Mcar was prominent in the brain.

Conclusions:

• Hagfish Mcrs exhibit broad ligand responsiveness and Mrap-independence, suggesting ancestral signaling.
• Functional receptors and tissue-specific expression imply physiological roles for melanocortin signaling in hagfish.
• Hagfish are valuable models for understanding the evolution of the vertebrate melanocortin system.