{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMYADM is a transmembrane protein of the MAL family that is ubiquitously expressed and possesses unique features including seven putative transmembrane segments. In human bone marrow, MYADM expression is widespread and is notably upregulated during hematopoietic differentiation – as observed in all‐trans retinoic acid–induced differentiation of promyelocytic leukemia cells – suggesting a role in cell fate decisions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, MYADM localizes in condensed plasma membrane domains and colocalizes with Rac1 in membrane protrusions, where it is essential for the incorporation of Rac1 into lipid rafts, thereby promoting proper membrane condensation, cell spreading, and directed cell migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn vascular contexts, MYADM contributes to the maintenance of endothelial integrity and vessel function. In human endothelial cells, MYADM is confined to ordered membrane domains that associate with filamentous actin and cell–cell junctions; loss of MYADM disrupts this organization, leading to increased permeability, upregulation of adhesion molecules such as ICAM-1, and enhanced leukocyte adhesion – processes that underpin an inflammatory phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Transcriptome analyses have also linked MYADM expression in monocytes to blood pressure variability, implicating it as one of several transcripts that together account for significant inter-individual differences in blood pressure."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, in pulmonary arterial hypertension (PAH), the miR-182-3p/MYADM axis regulates the proliferation of pulmonary artery smooth muscle cells by modulating the cell cycle inhibitor p21 via altered KLF4 localization, thereby contributing to vascular remodeling processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cell migration and vascular physiology, MYADM functions as a critical mediator in immune responses and viral pathogenesis. It has been identified as a binding partner for surfactant protein A (SP-A) on eosinophils, where the interaction with MYADM is required for SP-A–induced eosinophil apoptosis—a mechanism important for resolving airway inflammation in asthma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In a separate line of investigation, MYADM has emerged as an essential host factor for the entry of several human parechoviruses (PeV-A). Its extracellular domains, particularly a specific loop region, interact with viral capsid proteins to facilitate post-attachment viral entry, establishing MYADM as a multi-genotype receptor for these pathogens."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "W Cui, L Yu, H He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cloning of human myeloid-associated differentiation marker (MYADM) gene whose expression was up-regulated in NB4 cells induced by all-trans retinoic acid."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1023/a:1015288412047"}], "href": "https://doi.org/10.1023/a:1015288412047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12075932"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12075932"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Juan F Aranda, Natalia Reglero-Real, Leonor Kremer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MYADM regulates Rac1 targeting to ordered membranes required for cell spreading and migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E10-11-0910"}], "href": "https://doi.org/10.1091/mbc.E10-11-0910"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21325632"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21325632"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Juan F Aranda, Natalia Reglero-Real, Beatriz Marcos-Ramiro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MYADM controls endothelial barrier function through ERM-dependent regulation of ICAM-1 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E11-11-0914"}], "href": "https://doi.org/10.1091/mbc.E11-11-0914"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23264465"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23264465"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tanja Zeller, Claudia Schurmann, Katharina Schramm, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "MYADM binds human parechovirus 1 and is essential for viral entry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-024-47825-0"}], "href": "https://doi.org/10.1038/s41467-024-47825-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38658526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38658526"}]}]}]}