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MRAP2 regulates energy homeostasis by promoting primary cilia localization of MC4R

Adelaide Bernard1, Irene Ojeda Naharros2, Xinyu Yue1

  • 1Department of Medicine and The Diabetes Center.

JCI Insight
|January 24, 2023
PubMed

Insights

Melanocortin-4 receptor (MC4R) and MRAP2 protein are vital for controlling body weight. MRAP2 protein is crucial for MC4R

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • The melanocortin-4 receptor (MC4R) and its accessory protein MRAP2 regulate food intake and body weight.
  • MC4R functions within neuronal primary cilia, crucial organelles for signal transduction.

Purpose of the Study:

  • To investigate the role of MRAP2 in MC4R's weight-regulating function and ciliary localization.
  • To explore the general requirement of accessory proteins for G protein-coupled receptor (GPCR) ciliary localization.

Main Methods:

  • Utilized cellular and genetic models to study MC4R and MRAP2 interactions.
  • Investigated the localization of MC4R within neuronal primary cilia.

Main Results:

  • MRAP2 is essential for MC4R's role in regulating neuronal weight.
  • MRAP2 facilitates the localization of MC4R to neuronal primary cilia.
  • GPCR ciliary localization can depend on specific accessory proteins absent in standard cell cultures.

Conclusions:

  • Targeting MC4R to primary cilia is critical for long-term energy homeostasis.
  • Disruptions in MC4R ciliary localization may contribute to inherited obesity.
  • This study highlights the importance of accessory proteins for GPCR function in primary cilia.
Keywords:
EndocrinologyMelanocortinMetabolismNeuroendocrine regulationObesity

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