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Updated: Aug 4, 2025
12:38
Screening Peptides that Activate MRGPRX2 using Engineered HEK Cells
Published on: November 6, 2021
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Itch receptor MRGPRX4 interacts with the receptor activity-modifying proteins
Ilana B Kotliar1, Emilie Ceraudo2, Kevin Kemelmakher-Liben2
1Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University, New York, New York, USA; Tri-Institutional PhD Program in Chemical Biology, New York, New York, USA.
The Journal of Biological Chemistry
|April 1, 2023
Summary
Researchers found that Receptor Activity-Modifying Protein 2 (RAMP2) interacts with Mas-related GPCR subtype X4 (MRGPRX4). This interaction reduces signaling and cell surface expression, offering new therapeutic targets for cholestatic itch.
Area of Science:
- Biochemistry
- Pharmacology
- Hepatology
Background:
- Cholestatic itch is a severe symptom of liver disease with few treatments.
- Mas-related GPCR subtype X4 (MRGPRX4) is a bile acid receptor implicated in cholestatic itch.
- Receptor Activity-Modifying Proteins (RAMPs) modulate G protein-coupled receptor (GPCR) function.
Purpose of the Study:
- To investigate the interaction between MRGPRX4 and RAMPs.
- To determine the functional consequences of MRGPRX4-RAMP interactions.
- To predict the structural complex of MRGPRX4 and RAMP2.
Main Methods:
- Multiplexed immunoassay and proximity ligation assay to detect MRGPRX4-RAMP interactions.
- Quantitative NanoBRET pulse-chase assay to measure cell surface receptor expression.
- AlphaFold Multimer for structural complex prediction.
Main Results:
- MRGPRX4 interacts with RAMPs, specifically RAMP2.
- RAMP2 binding attenuates MRGPRX4 basal and agonist-dependent signaling.
- RAMP2 interaction decreases MRGPRX4 cell surface expression.
- The MRGPRX4-RAMP2 complex structure was predicted.
Conclusions:
- RAMP2 negatively regulates MRGPRX4 activity and expression.
- RAMP2's regulation of MRGPRX4 presents a potential therapeutic target for cholestatic itch.
- This discovery may lead to novel drug development strategies for liver disease-related pruritus.
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