{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nFormin homology domain-containing protein 3 (FHOD3) is a cardiac-restricted actin organizer that plays an essential role in assembling and reorganizing thin actin filaments into well‐ordered sarcomeres during heart development. In embryonic cardiomyocytes, FHOD3 functions via its conserved FH2 domain to promote actin polymerization and precise myofibrillogenesis, ensuring the proper formation and central organization of the sarcomere. Such activity is crucial to set the blueprint for subsequent cardiac contractile function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the postnatal and adult heart, FHOD3 continues to contribute to the maintenance and remodeling of sarcomeric structures. Its activity is tightly regulated by phosphorylation events—by kinases such as CK2 and ROCK—that modulate FHOD3’s localization, stability, and actin-forming capacity. For instance, phosphorylation by ROCK kinases relieves autoinhibition and stimulates actin filament synthesis, while aberrant regulation or misexpression of FHOD3 (including defective interactions with key binding partners like cardiac myosin-binding protein C) can lead to myofibrillar disarray and promote hypertrophic remodeling in response to stress. These regulatory processes underscore the protein’s dual role in preserving contractile integrity under normal conditions and in modulating pathological responses during cardiac hypertrophy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its central role in cardiac muscle, FHOD3 has been identified in other cellular contexts where precise actin dynamics determine cellular morphology and function. In specific subpopulations of cortical pyramidal neurons, FHOD3 localizes to dendritic spines and is critical for proper spine morphogenesis, suggesting a role in modulating synaptic transmission. Similarly, in auditory hair cells, balanced FHOD3 expression is essential for maintaining the integrity of the cuticular plate and stereocilia, with both overexpression and loss leading to structural defects and high-frequency hearing loss. These findings broaden the impact of FHOD3 from heart development and function to include key roles in neuronal and sensory cell architecture."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kenichiro Taniguchi, Ryu Takeya, Shiro Suetsugu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Crucial Role of ROCK2-Mediated Phosphorylation and Upregulation of FHOD3 in the Pathogenesis of Angiotensin II-Induced Cardiac Hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/HYPERTENSIONAHA.116.08662"}], "href": "https://doi.org/10.1161/HYPERTENSIONAHA.116.08662"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28438902"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28438902"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Tomoki Ushijima, Noriko Fujimoto, Sho Matsuyama, et al. 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