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  4. Pharmacological Evaluation of Melanocortin 2 Receptor Accessory Protein 2 on Axolotl Neural Melanocortin Signaling

Pharmacological Evaluation of Melanocortin 2 Receptor Accessory Protein 2 on Axolotl Neural Melanocortin Signaling

Frontiers in Endocrinology, 2022 · DOI: 10.3389/fendo.2022.820896 · Published: February 17, 2022

Regenerative MedicineEndocrinologyGenetics

Simple Explanation

The melanocortin system, involving receptors and accessory proteins, plays a crucial role in regulating appetite and energy balance. This study investigates this system in the axolotl, a salamander known for its regenerative abilities. Researchers cloned and analyzed genes related to melanocortin signaling in axolotls, finding similarities and differences compared to other species. They also examined how these genes are expressed in different tissues and how their expression changes during fasting. The study found that an accessory protein, MRAP2, affects the activity of melanocortin receptors in axolotls, influencing their function in regulating metabolism and energy homeostasis. This provides insights into the evolution and function of this important signaling pathway in a unique species.

Study Duration
3 Weeks
Participants
6 juvenile axolotls
Evidence Level
Not specified

Key Findings

  • 1
    Axolotl MC3R and MC4R can be activated by a-MSH and ACTH. Axolotl MC3R exhibited a high constitutive activity, that was significantly decreased by MRAP2
  • 2
    Axolotl MRAP2 significantly decreased the cell surface expression of MC4R in a dose-dependent manner but did not affect the trafficking of MC3R.
  • 3
    The study confirmed the direct interaction and co-localization of both MC3R and MC4R with MRAP2 proteins on the plasma membrane through co-IP and BiFC assays.

Research Summary

This study comprehensively examined and elucidated the pharmacological and physiological regulation of central melanocortin signaling in the axolotl. The study found a relatively conserved protein structure of axolotl MC3R, MC4R, and MRAP2 in comparison with other species, especially the TM regions. Pharmacological evaluation of the central melanocortin signaling of a primitive poikilotherm axolotl elucidated the vital physiological role in the regulation of appetite and energy balance in an amphibian species.

Practical Implications

Understanding Metabolic Regulation

The findings contribute to understanding the regulation of appetite and energy balance in a unique amphibian species, the axolotl.

Comparative Endocrinology

The study provides insights into the evolution and conservation of melanocortin signaling across different vertebrate species.

Potential Therapeutic Targets

The identification of MRAP2's role in modulating melanocortin receptor activity could inform the development of therapeutic strategies for metabolic disorders.

Study Limitations

  • 1
    Limited sample size in the food deprivation experiment.
  • 2
    The study is primarily in vitro, further in vivo studies are needed.
  • 3
    Lack of complete gene annotation of the axolotl genome.

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