Relaxin/insulin-like family peptide receptor 3

Relaxin/Insulin-like Family Peptide Receptor 3

The Relaxin/Insulin-like Family Peptide Receptor 3 (RXFP3) is a G-protein coupled receptor that plays a crucial role in various physiological processes. It is a member of the relaxin/insulin-like family peptide receptor subfamily, which also includes RXFP1 and RXFP2. RXFP3 is primarily expressed in the central nervous system and is involved in the regulation of stress responses, feeding behavior, and reproductive functions.

Structure

The RXFP3 receptor is encoded by the RXFP3 gene located on chromosome 4 in humans. It consists of seven transmembrane domains, an extracellular N-terminus, and an intracellular C-terminus. The extracellular domain contains the binding site for its ligands, which are the relaxin-3 peptides. The intracellular domain interacts with G-proteins to initiate downstream signaling pathways.

Ligands

The primary ligands for RXFP3 are the relaxin-3 peptides, which are derived from the preprorelaxin-3 precursor protein. Relaxin-3 is predominantly expressed in the brain, particularly in the nucleus incertus, a region involved in the regulation of stress and arousal. Upon binding to RXFP3, relaxin-3 peptides activate the receptor and initiate signaling cascades.

Functions

1. **Regulation of Stress Responses**: RXFP3 is involved in the modulation of stress responses. Activation of RXFP3 by relaxin-3 peptides leads to the inhibition of stress-related behaviors and the reduction of anxiety-like responses. This suggests that RXFP3 plays a role in the regulation of emotional states and stress coping mechanisms.

2. **Feeding Behavior**: RXFP3 is also implicated in the regulation of feeding behavior. Studies have shown that activation of RXFP3 by relaxin-3 peptides increases food intake, suggesting its involvement in appetite regulation. This receptor may be a potential target for the development of therapeutics for eating disorders and obesity.

3. **Reproductive Functions**: RXFP3 is expressed in regions of the brain involved in reproductive functions, such as the hypothalamus and pituitary gland. It is believed to play a role in the regulation of reproductive hormone release and sexual behavior. Further research is needed to fully understand the specific mechanisms by which RXFP3 influences reproductive functions.

Clinical Implications

Due to its involvement in various physiological processes, RXFP3 has gained attention as a potential therapeutic target for several disorders. Modulation of RXFP3 activity may have implications in the treatment of anxiety disorders, depression, eating disorders, and reproductive dysfunctions. However, further research is required to fully elucidate the therapeutic potential of targeting RXFP3.

References

1. Liu C, Eriste E, Sutton S, et al. Identification of relaxin-3/INSL7 as an endogenous ligand for the orphan G-protein-coupled receptor GPCR135. J Biol Chem. 2003;278(50):50754-50764. doi:10.1074/jbc.M308995200

2. Ma S, Bonaventure P, Ferraro T, Shen PJ, Burazin TC, Bathgate RA, et al. Relaxin-3 in GABA projection neurons of nucleus incertus suggests widespread influence on forebrain circuits via G-protein-coupled receptor-135 in the rat. Neuroscience. 2007;144(1):165-190. doi:10.1016/j.neuroscience.2006.08.070

3. Smith CM, Shen PJ, Banerjee A, et al. Distribution of relaxin-3 and RXFP3 within arousal, stress, affective, and cognitive circuits of mouse brain. J Comp Neurol. 2010;518(22):4016-4045. doi:10.1002/cne.22444