Journal article
The Melanocortin Receptor Accessory Protein 2 promotes food intake through inhibition of the Prokineticin Receptor-1
eLife, Vol.5(2016), e12397
02/01/2016
DOI: 10.7554/eLife.12397
PMCID: PMC4786424
PMID: 26829592
Abstract
The Melanocortin Receptor Accessory Protein 2 (MRAP2) is an important regulator of energy homeostasis and its loss causes severe obesity in rodents. MRAP2 mediates its action in part through the potentiation of the MC4R, however, it is clear that MRAP2 is expressed in tissues that do not express MC4R, and that the deletion of MRAP2 does not recapitulate the phenotype of Mc4r KO mice. Consequently, we hypothesized that other GPCRs involved in the control of energy homeostasis are likely to be regulated by MRAP2. In this study we identified PKR1 as the first non-melanocortin GPCR to be regulated by MRAP2. We show that MRAP2 significantly and specifically inhibits PKR1 signaling. We also demonstrate that PKR1 and MRAP2 co-localize in neurons and that Mrap2 KO mice are hypersensitive to PKR1 stimulation. This study not only identifies new partners of MRAP2 but also a new pathway through which MRAP2 regulates energy homeostasis.
The brain plays a major role in controlling how much food animals eat. The nerve cells (neurons) involved in this process contain “receptors” that respond to cues from various parts of the body. For example, a receptor called PKR1 acts to limit food intake. The activities of PKR1 and other receptors are tightly regulated in cells, but it is not clear how this works.A protein called MRAP2 is known to regulate the activity of a receptor that regulates food intake and energy use in the brain. However, MRAP2 may also interact with other receptors to control food intake. Here, Chaly, Srisai et al. investigated whether MRAP2 can regulate the activity of PKR1 in animal cells and rodents.The experiments show that MRAP2 can interact with and inhibit the activity of PKR1. Furthermore, both MRAP2 and PKR1 can be found in the same neurons. Mutant mice that lack the gene that encodes MRAP2 have higher levels of PKR1 activity and eat less than normal mice when PKR1 is stimulated. Together the experiments suggest that MRAP2 can increase food intake by preventing PKR1 from being activated in the brain. The next steps are to find out if this protein regulates other receptors involved in the control of food intake, and to test whether PKR1 and MRAP2 also play a role in regulating energy usage.
Details
- Title: Subtitle
- The Melanocortin Receptor Accessory Protein 2 promotes food intake through inhibition of the Prokineticin Receptor-1
- Creators
- Anna L Chaly - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, United States, Fraternal Order of Eagle Diabetes Research Center, University of Iowa, Iowa City, United States, Pappajohn Biomedical Institute, University of Iowa, Iowa City, United StatesDollada Srisai - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, United States, Fraternal Order of Eagle Diabetes Research Center, University of Iowa, Iowa City, United States, Pappajohn Biomedical Institute, University of Iowa, Iowa City, United StatesEllen E Gardner - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, United States, Fraternal Order of Eagle Diabetes Research Center, University of Iowa, Iowa City, United States, Pappajohn Biomedical Institute, University of Iowa, Iowa City, United StatesJulien A Sebag - Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, United States, Fraternal Order of Eagle Diabetes Research Center, University of Iowa, Iowa City, United States, Pappajohn Biomedical Institute, University of Iowa, Iowa City, United States
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.5(2016), e12397
- DOI
- 10.7554/eLife.12397
- PMID
- 26829592
- PMCID
- PMC4786424
- NLM abbreviation
- Elife
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Grant note
- name: Fraternal Order of Eagles Diabetes Research Center; name: Carver Trust Young Investigator award
- Language
- English
- Date published
- 02/01/2016
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984025685702771
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