Pharmacological modulation of the cAMP signaling of two isoforms of melanocortin-3 receptor by melanocortin receptor accessory proteins in the tetrapod Xenopus laevis

Endocrine Connections, 2021 · DOI: 10.1530/EC-21-0179 · Published: October 22, 2021

Simple Explanation

The melanocortin-3 receptor (MC3R) plays a crucial role in regulating energy balance. This study investigates how melanocortin receptor accessory proteins (MRAPs) influence the activity of two versions of MC3R in Xenopus laevis, a type of frog. The researchers found that MRAP2 proteins can enhance the signaling of MC3Rs when stimulated and reduce the amount of MC3R on the cell surface. A similar effect was observed with MRAP1 on one version of MC3R. These findings help understand how the melanocortin system functions in animals with duplicated genes and how this system has remained consistent throughout evolution.

Study Duration

Not specified

Participants

Adult male Xenopus laevis (2 years old), HEK293T cells

Evidence Level

In vitro study

Key Findings

1
xlMRAP2.L/S enhances α-MSH-stimulated xlMC3Rs signaling and reduces their surface expression.
2
xlMC3R.L exhibits similar ligand and surface expression profiles in the presence of xlMRAP1.L.
3
The distinct pharmacological modulation of xlMC3R.L and xlMC3R.S by dual MRAP2 proteins elucidates the functional consistency of the melanocortin system during genomic duplication.

Research Summary

This study investigates the evolutionary conservation and functional divergence of two homologous MC3Rs in the allotetraploid frog Xenopus laevis in vitro. The study clarified the interaction between xlMC3Rs and xlMRAPs, showing the protein complex located on the plasma membrane by bimolecular fluorescence complementation analysis in vitro. Distinct pharmacological profiles in vitro with different gene combinations of MC3R and MRAPs in Xenopus laevis and Xenopus tropicalis spurred us to further focus on the evolutionary conservation and variability of MCRs functions in vivo in amphibians.

Practical Implications

Understanding Gene Duplication

The study provides insights into the functional consistency of the melanocortin system during genomic duplication in tetrapod vertebrates.

Drug Development

These findings could aid in developing targeted therapies for metabolic disorders by modulating MC3R signaling through MRAPs.

Comparative Physiology

The research highlights the importance of studying the melanocortin system in diverse species like Xenopus laevis to understand its evolutionary conservation and functional variability.

Study Limitations

1
The study is conducted in vitro and may not fully reflect the complexity of the melanocortin system in vivo.
2
The precise mechanisms by which MRAPs modulate MC3R signaling and surface expression require further investigation.
3
The study focuses on Xenopus laevis, and further research is needed to determine the generalizability of these findings to other species.

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