Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity

M Asai, S Ramachandrappa, M Joachim, Y Shen… - Science, 2013 - science.org
M Asai, S Ramachandrappa, M Joachim, Y Shen, R Zhang, N Nuthalapati, V Ramanathan…
Science, 2013science.org
Melanocortin receptor accessory proteins (MRAPs) modulate signaling of melanocortin
receptors in vitro. To investigate the physiological role of brain-expressed melanocortin 2
receptor accessory protein 2 (MRAP2), we characterized mice with whole-body and brain-
specific targeted deletion of Mrap2, both of which develop severe obesity at a young age.
Mrap2 interacts directly with melanocortin 4 receptor (Mc4r), a protein previously implicated
in mammalian obesity, and it enhances Mc4r-mediated generation of the second messenger …
Melanocortin receptor accessory proteins (MRAPs) modulate signaling of melanocortin receptors in vitro. To investigate the physiological role of brain-expressed melanocortin 2 receptor accessory protein 2 (MRAP2), we characterized mice with whole-body and brain-specific targeted deletion of Mrap2, both of which develop severe obesity at a young age. Mrap2 interacts directly with melanocortin 4 receptor (Mc4r), a protein previously implicated in mammalian obesity, and it enhances Mc4r-mediated generation of the second messenger cyclic adenosine monophosphate, suggesting that alterations in Mc4r signaling may be one mechanism underlying the association between Mrap2 disruption and obesity. In a study of humans with severe, early-onset obesity, we found four rare, potentially pathogenic genetic variants in MRAP2, suggesting that the gene may also contribute to body weight regulation in humans.
AAAS