MS4A2 Membrane Protein Introduction

Introduction of MS4A2

High-affinity immunoglobulin epsilon receptor subunit beta is a protein that in humans is encoded by the MS4A2 gene. MS4A2 is an IgE receptor found on the surface of mast cells and basophils, composed of α, β, and two disulfide-linked γ chains. It recognizes the beta subunit of the high-affinity IgE receptor and binds to the Fc region of immunoglobulin epsilon. In addition, MS4A2 is a member of the membrane-spanning 4A gene family, which shares common structural features.

Function of MS4A2 Membrane Protein

MS4A2 is a high-affinity receptor that binds to the Fc region of immunoglobulin epsilon. It regulates the response of mast cell responses by the aggregation of FCER1 by multivalent antigens, including the release of preformed mediators (such as histamine) by degranulation and de novo production of lipid mediators and cytokines. MS4A2 also mediates the secretion of important lymphokines. In addition, it also regulates allergic disease signaling pathways by binding of allergens to receptor-bound IgE, resulting in activation of cells and release of mediators that cause allergic manifestations. Moreover, MS4A2 is expressed on the surface of mast cells and basophils and shows a unique expression pattern in hematopoietic and non-lymphoid tissues. Several variants within MS4A gene cluster have been implicated the association of Alzheimer's disease (AD) by serial recent genome-wide association studies (GWAS). As a cell membrane protein, MS4A2 has been also found to be involved in the regulation of calcium signaling, which has been extensively discussed in neurodegeneration and AD.

Fig.1 The proposed roles of MS4A2 in mast cell function. (Bradding, 2015)

Application of MS4A2 Membrane Protein in Literature

1. Ferreira M.A., et al. Characterization of the methylation patterns of MS4A2 in atopic cases and controls. Allergy. 2010, 65(3):333-337. PubMed ID: 19796196
   
   

   The study investigated the methylation patterns of key genes in the allergic cascade including the transmembrane 4-domains, subfamily A, and member 2 genes (MS4A2), and analyzed its role in allergic diseases.

2. Wilson B.S., et al. FcεRI signaling observed from the inside of the mast cell membrane. Molecular Immunology. 2002, 38(16):1259-1268. PubMed ID: 12217393
   
   

   The authors found that the high-affinity IgE receptor, FcrepsilonRI, on basophils and mast cells initiated cascades of biochemical events leading to degranulation, membrane ruffling and other physiological responses, which offers a new idea for developing new targets for the treatment of allergies and asthma.

3. Hendricks-Taylor L.R., et al. SLP-76 is a substrate of the high affinity IgE receptor-stimulated protein tyrosine kinases in rat basophilic leukemia cells. Journal of Biological Chemistry. 1997, 272(2):1363-1367. PubMed ID: 8995445
   
   

   This report demonstrated that phosphorylation of SLP-76 required Syk activity, but did not rely on Ca²⁺ mobilization, and that SLP-76 and its associated proteins may be involved in signaling events in multiple cell types in the immune system.

4. Inage E., et al. Critical roles for PU.1, GATA1, and GATA2 in the expression of human FcεRI on mast cells: PU.1 and GATA1 transactivate FCER1A, and GATA2 transactivates FCER1A and MS4A2. Journal of Immunology. 2014, 192(8):3936-3946. PubMed ID: 24639354
   
   

   The article suggested that PU.1 and GATA1 participated in FcεRIα transcription by recruiting its promoters and GATA2 positively regulates FcεRIβ transcription. Inhibition of these transcription factors results in the down-regulated FcεRI expression and IgE-mediated degranulation activity.

5. Ma J., et al. MS4A cluster in Alzheimer's disease. Molecular Neurobiology. 2015, 51(3):1240-1248. PubMed ID: 24981432
   
   

   The authors summarized the structure, localization, and function of the MS4A gene cluster, reviewed the recent genetic and expression findings of the MS4A gene cluster associated with the pathogenesis of AD, and speculated on the possible role of the MS4A gene cluster in this disease.

MS4A2 Preparation Options

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Reference

1. Bradding P and Arthur G. (2015). Mast cells in Asthma state of the art. Clinical & Experimental Allergy Journal of the British Society for Allergy & Clinical Immunology. 46(2), 194-263.

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