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Publication : MRAP2 regulates energy homeostasis by promoting primary cilia localization of MC4R.

First Author  Bernard A Year  2023
Journal  JCI Insight Volume  8
Issue  2 PubMed ID  36692018
Mgi Jnum  J:336317 Mgi Id  MGI:7441396
Doi  10.1172/jci.insight.155900 Citation  Bernard A, et al. (2023) MRAP2 regulates energy homeostasis by promoting primary cilia localization of MC4R. JCI Insight 8(2)
abstractText  The G protein-coupled receptor melanocortin-4 receptor (MC4R) and its associated protein melanocortin receptor-associated protein 2 (MRAP2) are essential for the regulation of food intake and body weight in humans. MC4R localizes and functions at the neuronal primary cilium, a microtubule-based organelle that senses and relays extracellular signals. Here, we demonstrate that MRAP2 is critical for the weight-regulating function of MC4R neurons and the ciliary localization of MC4R. More generally, our study also reveals that GPCR localization to primary cilia can require specific accessory proteins that may not be present in heterologous cell culture systems. Our findings further demonstrate that targeting of MC4R to neuronal primary cilia is essential for the control of long-term energy homeostasis and suggest that genetic disruption of MC4R ciliary localization may frequently underlie inherited forms of obesity.
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