MRGPRX2

What is MRGPRX2 protein?

MRGPRX2 stands for Mas-related GPR family member X2. It is a G protein-coupled receptor (GPCR) protein that is expressed highly in sensory neurons in the dorsal root ganglia and trigeminal ganglia.

It belongs to the MRG (Mas-related G protein-coupled) receptor family which detects pruritogens (itch-causing substances). MRGPRX2 acts as a receptor for pruritogens such as chloroquine, histamine, BAM8-22 peptide, etc. Its activation leads to itch sensation. When activated by ligands, MRGPRX2 couples to Gα14 subunit of G protein and activates downstream signaling pathways like PLCβ-IP3/DAG pathway. This ultimately leads to depolarization of sensory neurons. Genetic ablation or inhibition of MRGPRX2 reduces itch responses induced by various pruritogens, suggesting its crucial role in itch transmission. It is expressed in nearly all neurons of the dorsal root ganglia that respond to itch. So it functions as a key receptor for detection and transmission of itch sensory signals from the skin to the central nervous system. Dysregulation or mutations in MRGPRX2 have been linked to chronic itch/pruritus conditions like atopic dermatitis and cholestatic pruritus.

MRGPRX2 is an important GPCR that acts as the main receptor for detection and transmission of itch sensation mediated by various pruritogens through peripheral sensory neurons. Understanding its function and regulation is valuable for developing anti-itch therapies.

What is the function of MRGPRX2 protein?

MRGPRX2 functions as a key receptor located on the peripheral terminals of pruriceptors to sense pruritogens and trigger intracellular signaling that leads to itch perception via the nervous system.The main function of MRGPRX2 is to act as a receptor for pruritogens on sensory neurons and mediate the detection and transmission of itch signals from the periphery to the CNS. This makes it central to the itch sensation pathway.

MRGPRX2 related signaling pathway

MRGPRX2 couples to Gα14 to activate PLCβ/IP3 and DAG pathways, resulting in increase in intracellular Ca2+ and PKC activation. This modulates ion channels and generates action potentials to transmit pruritic signals to the CNS.

MRGPRX2 Related Diseases

•  Atopic dermatitis (eczema): Mice deficient in Mrgprx2 show reduced itch induced by atopic dermatitis-like skin lesions. It suggests a role in atopic dermatitis-related chronic itch.
•  Chronic cholestatic pruritus: Itch is a common symptom of cholestasis. Patients with elevated bile acids show increased MRGPRX2 expression. Bile acids may activate MRGPRX2 to induce itch.
•  Histamine-dependent itch: MRGPRX2 is crucial for histamine-induced itch. Mice lacking Mrgprx2 are resistant to acute itch from intravenous histamine.
•  Chronic idiopathic pruritus: Polymorphisms in the MRGPRX2 gene were found to correlate with chronic idiopathic pruritus in Chinese population.
•  Drug target for anti-itch medications: Inhibiting MRGPRX2 activity/signaling could provide relief from itch in various dermatological and systemic diseases involving chronic itch. Many antagonists are under research.
•  Biomarker for diagnosing itchy conditions: Monitoring temporal changes in MRGPRX2 expression levels in skin/blood could aid diagnosis of diseases presenting with pruritus like eczema, liver disorders etc.
•  Screening new anti-pruritic drugs: High-throughput screening using assays measuring MRGPRX2 activation/signaling can help identify novel therapeutic molecules to target chronic itch.

Biomedical Application of MRGPRX2 Protein

•  Drug target for anti-itch medications: Inhibiting MRGPRX2 activity/signaling could provide relief from itch in various dermatological and systemic diseases involving chronic itch. Many antagonists are under research.
•  Gene therapy approach: Over-expressing anti-itch microRNAs or delivering therapeutic genes locally that suppress MRGPRX2 levels may alleviate persistent itch conditions.
•  Itch pathway dissection: Using mouse models with Mrgprx2 knockout or overexpression helps elucidate ligand-receptor interactions and complex neuronal pathways behind itch sensation.

•  Itch pathway dissection: Using mouse models with Mrgprx2 knockout or overexpression helps elucidate ligand-receptor interactions and complex neuronal pathways behind itch sensation.
•  Screening new anti-pruritic drugs: High-throughput screening using assays measuring MRGPRX2 activation/signaling can help identify novel therapeutic molecules to target chronic itch.