{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMYO18A is an unconventional myosin that plays a critical role at the Golgi apparatus by mechanically linking membranes to the actin cytoskeleton. Its binding to the phosphatidylinositol‐4‐phosphate–enriched protein GOLPH3 enables the generation of a tensile force that is required for efficient vesicle and tubule formation, thereby maintaining Golgi architecture. Moreover, following DNA damage, enhanced GOLPH3 phosphorylation increases MYO18A engagement, leading to Golgi dispersal and supporting cell survival pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, MYO18A contains two distinct actin‐binding sites. One is located within its unique, lysine/glutamate–rich N‐terminal extension and binds F‑actin in an ATP‐insensitive manner, while the second site, embedded in its conserved motor domain, exhibits nucleotide‐dependent regulation. Its ability to dimerize via a segmented coiled‑coil region further endows MYO18A with the capacity to cross‑link actin filaments and contribute to the higher‐order organization of the cytoskeleton."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its structural functions, MYO18A participates in the regulation of cell motility. By interacting with the PAK2 signaling complex through the betaPIX/GIT1 adaptor, MYO18A localizes to lamellipodia and ruffling membranes, thereby influencing actin dynamics and epithelial cell migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe activity of MYO18A is also modulated by related proteins. For example, the paralogue GOLPH3L, which is unable to robustly bind MYO18A, antagonizes the functional linkage between GOLPH3 and MYO18A at the Golgi, thereby impacting vesicular trafficking and Golgi morphology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn certain hematologic malignancies, chromosomal rearrangements yield a fusion between MYO18A and the platelet‐derived growth factor receptor β gene (PDGFRB). This MYO18A‑PDGFRB fusion is associated with eosinophilia‐related myeloproliferative neoplasms that respond well to imatinib therapy, underscoring the pathological potential of aberrant MYO18A activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlternative splicing of the MYO18A transcript produces isoforms that function as receptors. Notably, the SP‑R210 isoform serves as a receptor for surfactant protein A (SP‑A), mediating immunomodulatory effects. Engagement of SP‑R210 alters lymphocyte activation and cytokine secretion, and in macrophages, it modulates antiviral responses and macropinocytic sorting of viral particles."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMYO18A further contributes to immune receptor signaling in B cells by partnering with the adaptor protein ezrin. Upon B cell receptor stimulation, MYO18A co‐segregates with the receptor and phosphotyrosine‐rich complexes, suggesting that the MYO18A–ezrin complex may help orchestrate the assembly of signalosomes that amplify antigen‐dependent signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTogether with its roles in linking membranes to the actin cytoskeleton and organizing signaling complexes, MYO18A is acknowledged as a divergent member of the myosin superfamily that impacts multiple cellular processes including vesicular trafficking, cell migration, and immune regulation. Its diverse functions and involvement in oncogenic fusions further highlight MYO18A as a potential cancer driver."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Holly C Dippold, Michelle M Ng, Suzette E Farber-Katz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the Golgi to promote budding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2009.07.052"}], "href": "https://doi.org/10.1016/j.cell.2009.07.052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19837035"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19837035"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Suzette E Farber-Katz, Holly C Dippold, Matthew D Buschman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA damage triggers Golgi dispersal via DNA-PK and GOLPH3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2013.12.023"}], "href": "https://doi.org/10.1016/j.cell.2013.12.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24485452"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24485452"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yasushi Isogawa, Takahide Kon, Takeshi Inoue, et al. 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