{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZyxin is a versatile focal adhesion protein that couples extracellular signals with cytoskeletal organization. Early studies using zyxin‐null fibroblasts revealed that loss of zyxin enhances integrin‐dependent adhesion and alters actomyosin contractility, thereby affecting stress fiber assembly and turnover. In addition, novel binding partners—such as LIM‐nebulette and Tes—have been identified, underscoring zyxin’s role in nucleating and modulating the assembly and dynamics of focal adhesions and associated actin structures. These findings collectively indicate that zyxin is essential for proper actin remodeling and for bridging adhesion receptors to the actin cytoskeleton."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn diverse contexts, zyxin regulates cell migration, epithelial–mesenchymal transition (EMT) and oncogenic signaling. For instance, TGF‑β– and Twist1‐driven upregulation of zyxin mediates actin reorganization and enhanced motility during EMT, while in lung and colon cancer models zyxin acts downstream of Smad‑dependent TGF‑β signals and cooperates with regulators such as CDK8 to modulate YAP activity and tumor progression. Moreover, transcription factors like Tead2 help redistribute key co‐activators in the nucleus by promoting zyxin expression, thereby influencing the invasive and metastatic potential of cancer cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical role at focal adhesions, zyxin is critical for specialized cellular responses to mechanical stimuli in a range of tissues. In endothelial cells, zyxin promotes the final stages of secretory granule (Weibel–Palade body) exocytosis through local actin reorganization. In the kidney and heart, zyxin contributes to cell–cell junction integrity and mechanosensitive survival pathways, with its loss predisposing to podocyte foot process effacement, fibrosis and cardiomyocyte apoptosis under stress. In megakaryocytes, zyxin supports proplatelet formation by maintaining the surface expression of key glycoproteins via VASP‐mediated cytoskeletal organization. Furthermore, genome‐wide studies have implicated variants of FAM155A—a protein that not only functions as an auxiliary subunit of the NALCN sodium leak channel by forming an extracellular dome to protect its ion‐selectivity filter but is also associated with reduced risk of diverticulitis—in highlighting a broader network of mechanotransduction and ion permeation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Laura M Hoffman, David A Nix, Beverly Benson, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Genetic ablation of zyxin causes Mena/VASP mislocalization, increased motility, and deficits in actin remodeling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200512115"}], "href": "https://doi.org/10.1083/jcb.200512115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16505170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16505170"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Laura M Hoffman, Christopher C Jensen, Aashi Chaturvedi, et al. 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