Structural insights into MRGPRX2: A new vision of itch and allergy

Trier, Anna M.; Kim, Brian

doi:10.1016/j.jaci.2022.01.017

Cited by 8 publications

(4 citation statements)

References 10 publications

(23 reference statements)

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“…The RAMPs may further regulate MRGPRX4 by promoting or disrupting its heterodimerization. Finally, other Mas-related family members MRGPRX1 and MRGPRX2 might also modulate itch ( 1 , 42 , 43 , 44 , 45 ). The discovery of MRGPRX4–RAMP interactions raises the intriguing possibility that other itch receptors from the same family may also interact with the RAMPs.…”

Section: Discussionmentioning

confidence: 99%

Itch receptor MRGPRX4 interacts with the receptor activity–modifying proteins

Kotliar¹,

Ceraudo²,

Kemelmakher-Liben³

et al. 2023

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Itch receptor MRGPRX4 interacts with the receptor activity–modifying proteins

Kotliar¹,

Ceraudo²,

Kemelmakher-Liben³

et al. 2023

Journal of Biological Chemistry

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“…Apart from IgE/FcεRI-dependent signaling, IgEindependent pathways have increasingly been studied 20 . Mas-related G protein-coupled receptor X2 (MRGPRX2), for example, is an unselective receptor binding to many different agonists including endogenous neuropeptides (substance P), innate antimicrobial peptides, eosinophil granule proteins, and numerous synthetic drugs, such as codeine, some NSAIDs, and fluorquinolones 21 . Blocking MRGPRX2 seems promising not only for CSU but also for atopic dermatitis (AD), allergic contact dermatitis, non-histaminergic itch, and small molecule compound-induced pseudoallergy 20 .…”

Section: The Central Role Of Mast Cellsmentioning

confidence: 99%

Omalizumab and new therapeutic targets in chronic spontaneous urticaria

Pereira,

Xará,

Flor

et al. 2024

PJDV

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Chronic spontaneous urticaria (CSU) is a common and distressing skin disease characterized by itchy wheals, angioedema, or both. There is currently no cure for CSU and symptomatic treatment is often insufficient. Omalizumab, a humanized anti-immunoglobulin (Ig) E monoclonal antibody, remains the only biological drug licensed for CSU, almost a decade after its approval. However, growing knowledge of the pathophysiological mechanisms of this disease has led to recent advances in its treatment, with several drugs in investigation both in pre-clinical and clinical settings. These include biologicals, such as dupilumab (anti-IL-4Rα), secukinumab (anti-IL-17), tezepelumab (anti-TSLP), ligelizumab (anti-IgE), lirentelumab (anti-Siglet 8), and barzovolimab (anti-cKIT), as well as "small molecules," such as Bruton tyrosine kinase (BTK) inhibitors (remibrutinib) and a Mas-related G protein-coupled receptor X2 (MRGPRX2) antagonist. Here, we review the current and future therapeutic options for CSU, based on what is known about the pathogenesis of the disease.

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“…Other GPCRs are also shown to modulate itch response, including the Masrelated family members MRGPRX1 and MRGPRX2 1,50,[52][53][54] . The four MRGPRX subtypes (X1-X4) are closely related and, except for orphan MRGPRX3 for which very little is known, they all are considered itch receptors.…”

Section: Ramp2 Has Been Reported To Have Pleiotropic Effects On G Pro...mentioning

confidence: 99%

Itch receptor MRGPRX4 interacts with the receptor activity-modifying proteins (RAMPs)

Kotliar

Ceraudo

Kemelmakher-Liben

et al. 2022

Preprint

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Cholestatic itch is a severe and debilitating symptom in liver diseases with limited treatment options. The class A G protein-coupled receptor (GPCR) Mas-related GPCR subtype X4 (MRGPRX4) has been identified as a receptor for bile acids, which are potential cholestatic pruritogens. An increasing number of GPCRs have been shown to interact with receptor activity-modifying proteins (RAMPs), which can modulate different aspects of GPCR biology. Using a combination of multiplexed immunoassay and proximity ligation assay we show that MRGPRX4 interacts with RAMPs. The interaction of MRGPRX4 with RAMP2, but not RAMP1 or 3, causes attenuation of basal and agonist-dependent signaling, which correlates with a decrease of MRGPRX4 cell surface expression as measured using a quantitative NanoBRET pulse-chase assay. Finally, we use AlphaFold Multimer to predict the structure of the MRGPRX4-RAMP2 complex. The discovery that RAMP2 regulates MRGPRX4 may have direct implications for future drug development for cholestatic itch.

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Structural insights into MRGPRX2: A new vision of itch and allergy

Cited by 8 publications

References 10 publications

Itch receptor MRGPRX4 interacts with the receptor activity–modifying proteins

Itch receptor MRGPRX4 interacts with the receptor activity–modifying proteins

Omalizumab and new therapeutic targets in chronic spontaneous urticaria

Itch receptor MRGPRX4 interacts with the receptor activity-modifying proteins (RAMPs)

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