{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMYO7A is an unconventional actin‐based motor protein that plays a pivotal role in sensory hair cells by translocating key adaptor proteins—such as harmonin and cadherin‑23—along the actin cores of developing stereocilia. This transport is essential for the maintenance of stereocilia cohesion and proper mechanotransduction, as demonstrated by its impaired function in mutant mice and rat models where disruption of MYO7A leads to disorganized hair bundles and consequent deafness."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBiochemical and biophysical studies have revealed that MYO7A’s motor properties are finely regulated by its structural conformation and interactions with accessory proteins. Its autoinhibited “tail‐inhibited” conformation, which can be relieved upon cargo binding or via induced dimerization, permits the enzyme to achieve a high duty ratio and slow, processive movement along actin filaments. Mutations in critical regions—such as within the IQ motifs that mediate calmodulin binding or in the motor domain that fuels ATPase activity—disrupt these regulatory mechanisms, leading to decreased ATPase activity, impaired cargo transport, and a lower effective duty ratio."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the retina, MYO7A serves a dual role by contributing to the maintenance of photoreceptor and retinal pigment epithelial cell integrity through its involvement in intracellular transport processes—such as lysosomal trafficking—and by facilitating organized protein distribution essential for visual function. Functional gene delivery using adeno‐associated viral vectors and correction of MYO7A mutations in induced pluripotent stem cells have both demonstrated restoration of normal stereocilia organization and electrophysiological properties, underscoring its therapeutic potential. Moreover, the differential impact of mutations—as seen in cases of residual function in nonsyndromic hearing loss (DFNB2) versus more severe Usher syndrome type 1B—highlights the importance of precise MYO7A motor function in sensory maintenance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Batiste Boëda, Aziz El-Amraoui, Amel Bahloul, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Impacts of Usher syndrome type IB mutations on human myosin VIIa motor function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi8007142"}], "href": "https://doi.org/10.1021/bi8007142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18700726"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18700726"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yi Sun, Jing Chen, Hanjun Sun, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Mutation spectrum of MYO7A and evaluation of a novel nonsyndromic deafness DFNB2 allele with residual function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.20677"}], "href": "https://doi.org/10.1002/humu.20677"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18181211"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18181211"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Samuel G Jacobson, Artur V Cideciyan, Tomas S Aleman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Usher syndromes due to MYO7A, PCDH15, USH2A or GPR98 mutations share retinal disease mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddn140"}], "href": "https://doi.org/10.1093/hmg/ddn140"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18463160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18463160"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "V S Lopes, S E Boye, C M Louie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Retinal gene therapy with a large MYO7A cDNA using adeno-associated virus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene Ther (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/gt.2013.3"}], "href": "https://doi.org/10.1038/gt.2013.3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23344065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23344065"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Zi-Hua Tang, Jia-Rong Chen, Jing Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Correction of Induced Pluripotent Stem Cells From a Deaf Patient With MYO7A Mutation Results in Morphologic and Functional Recovery of the Derived Hair Cell-Like Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells Transl Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.5966/sctm.2015-0252"}], "href": "https://doi.org/10.5966/sctm.2015-0252"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27013738"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27013738"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Lily E Soni, Carmen M Warren, Cecilia Bucci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The unconventional myosin-VIIa associates with lysosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Motil Cytoskeleton (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cm.20080"}], "href": "https://doi.org/10.1002/cm.20080"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16001398"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16001398"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "P Roman-Naranjo, M D C Moleon, I Aran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rare coding variants involving MYO7A and other genes encoding stereocilia link proteins in familial meniere disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hear Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.heares.2021.108329"}], "href": "https://doi.org/10.1016/j.heares.2021.108329"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34391192"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34391192"}]}]}]}