The M3 Muscarinic Acetylcholine Receptor Promotes Epidermal Differentiation

Duan, Junyan; Grando, Charles; Liu, Shuman; Chernyavsky, Alexander I.; Chen, Jefferson K.; Andersen, Bogi; Grando, Sergei A.

doi:10.1016/j.jid.2022.06.013

Cited by 4 publications

(3 citation statements)

References 46 publications

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“…M3 mAChR knockout mice ( Chmr3 −/− are noted to have an altered intercellular cohesion of basal cells, epidermal hyperplasia, and modulation of genes that contribute to intercellular adhesion and cell arrangement [ 29 ]. Notably, Chmr3 −/− mice and patients with PV both display an altered epidermal morphology [ 29 ]. Most recently, our team characterized the cellular and molecular mechanisms by which M3 mAChR controls the epidermal structure and function.…”

Section: Anti-achr Autoimmunity In Pemphigusmentioning

confidence: 99%

The Role of Non-Neuronal Acetylcholine in the Autoimmune Blistering Disease Pemphigus Vulgaris

Foulad

Cirillo

Grando

2023

Biology

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The importance of acetylcholine (ACh) in keratinocyte adhesion and acantholysis has been investigated over the last three decades, particularly in the pathophysiology of autoimmune blistering dermatoses. Pemphigus vulgaris (PV) is an autoimmune blistering skin disease where autoantibody-mediated suprabasilar intraepidermal splitting causes flaccid blisters and non-healing erosions of the oral mucosa and sometimes also of the skin. Historically, acantholysis in PV was thought to be driven by anti-desmoglein (Dsg) antibodies. Herein, we describe the role of autoantibodies against keratinocyte muscarinic and nicotinic acetylcholine receptors, as well as the annexin-like molecule pemphaxin that also binds ACh, in the immunopathogenesis of PV. The identification of targets in this disease is important, as they may lead to novel diagnostic and therapeutic options in the future for this potentially deadly disease.

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Section: Anti-achr Autoimmunity In Pemphigusmentioning

confidence: 99%

The Role of Non-Neuronal Acetylcholine in the Autoimmune Blistering Disease Pemphigus Vulgaris

Foulad

Cirillo

Grando

2023

Biology

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“…The M 3 R is one of the five muscarinic GPCRs (M1-M5) to which acetylcholine binds to initiate cellular responses (Kruse et al, 2014a). For the M 3 R, physiological responses include vasoconstriction, bronchoconstriction, insulin secretion, visual accommodation, and epidermal differentiation (Duan et al, 2022;Duttaroy et al, 2004;Kruse et al, 2014b). The M 3 R is expressed in a wide variety of tissues, including smooth muscle and pancreatic beta cells, as well as immune cells such B cells and T cells where their function is not yet clearly established (Kawashima and Fujii, 2004;Wess, 2004).…”

Section: Introductionmentioning

confidence: 99%

The M3 muscarinic acetylcholine receptor can signal through multiple G protein families

Smith,

Hilibrand,

Skiba

et al. 2024

Mol Pharmacol

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The M3 muscarinic acetylcholine receptor (M 3 R) is a G protein coupled receptor (GPCR) that regulates important physiological processes including vascular tone, bronchoconstriction, and insulin secretion. It is expressed on a wide variety of cell types, including pancreatic beta, smooth muscle, neuronal, and immune cells. Agonist binding to the M 3 R is thought to initiate intracellular signaling events primarily through the heterotrimeric G protein Gq. However, reports differ on the ability of M 3 R to couple to other G proteins beyond Gq. Using members from the four primary G protein families (Gq, Gi, Gs, and G13) in radioligand binding, GTP turnover experiments, and cellular signaling assays including live cell G protein dissociation and second messenger assessment of cAMP and inositol trisphosphate, we show that other G protein families, particularly Gi and Gs, can also interact with the human M 3 R. We further show that these interactions are productive as assessed by amplification of classical second messenger signaling events. Our findings demonstrate that the M 3 R is more promiscuous with respect to G protein interactions than previously appreciated.

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“…It consists of a single exon and contains over 1100 single nucleotide polymorphisms (SNPs), making it the most polymorphic gene among the muscarinic receptors. 20 , 21 A growing body of evidence suggests that missense mutations in the CHRM3 gene are functionally associated with increased BP due to enhanced signaling and re‐sensitization of M3R. These mutations also promote the production of epinephrine.…”

Section: Introductionmentioning

confidence: 99%

Associations of genetic variations in the M3 receptor with salt sensitivity, longitudinal changes in blood pressure and the incidence of hypertension in Chinese adults

Zhang,

Yao,

Bao

et al. 2023

J of Clinical Hypertension

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Recent studies have reported the role of the M3 muscarinic acetylcholine receptor (M3R), a member of the G‐protein coupled receptor superfamily, encoded by the CHRM3 gene, in cardiac function and the regulation of blood pressure (BP). The aim of this study was to investigate the associations of CHRM3 genetic variants with salt sensitivity, longitudinal BP changes, and the development of hypertension in a Chinese population. We conducted a chronic dietary salt intervention experiment in a previously established Chinese cohort to analyze salt sensitivity of BP. Additionally, a 14‐year follow‐up was conducted on all participants in the cohort to evaluate the associations of CHRM3 polymorphisms with longitudinal BP changes, as well as the incidence of hypertension. The single nucleotide polymorphism (SNP) rs10802811 within the CHRM3 gene displayed significant associations with low salt‐induced changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), while rs373288072, rs114677844, and rs663148 exhibited significant associations with SBP and MAP responses to a high‐salt diet. Furthermore, the SNP rs58359377 was associated with changes in SBP and pulse pressure (PP) over the course of 14 years. Additionally, the 14‐year follow‐up revealed a significant association between the rs619288 polymorphism and an increased risk of hypertension (OR = 1.74, 95% CI: 1.06‐2.87, p = .029). This study provides evidence that CHRM3 may have a role in salt sensitivity, BP progression, and the development of hypertension.

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The M3 Muscarinic Acetylcholine Receptor Promotes Epidermal Differentiation

Cited by 4 publications

References 46 publications

The Role of Non-Neuronal Acetylcholine in the Autoimmune Blistering Disease Pemphigus Vulgaris

The Role of Non-Neuronal Acetylcholine in the Autoimmune Blistering Disease Pemphigus Vulgaris

The M3 muscarinic acetylcholine receptor can signal through multiple G protein families

Associations of genetic variations in the M3 receptor with salt sensitivity, longitudinal changes in blood pressure and the incidence of hypertension in Chinese adults

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