{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe provided abstracts focus on transmembrane inner ear protein (TMIE), a critical component of the mechanotransduction machinery in auditory hair cells. TMIE is essential for normal hearing because its loss or mutation disrupts the formation and proper function of the mechanotransduction complex. In mouse models, deletion or truncating mutations of the TMIE gene lead to abnormal hair cell stereocilia and consequent hearing loss as well as vestibular dysfunction, underscoring its vital role in the development, maturation, and maintenance of inner ear structures."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n\nFurthermore, TMIE acts at the molecular level as an indispensable subunit of the mechanotransduction channel complex. It not only forms a ternary complex with tip-link molecules such as protocadherin 15 (PCDH15) and its binding partner TMHS/LHFPL5 but also physically interacts with the channel-forming TMC1/2 proteins. Notably, the C-terminal domain of TMIE engages in phospholipid interactions (for example, with PIP2), which appear to modulate ion channel properties including unitary conductance and ion selectivity. Additionally, alternative splicing events in TMIE and its associated proteins further diversify the compositions of the mechanotransduction complex, suggesting an additional layer of regulation in auditory function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n\nFinally, studies employing tmie-overexpression in transgenic mouse models demonstrate that restoring appropriate levels of TMIE can ameliorate the behavioral and auditory deficits caused by its loss. This therapeutic rescue emphasizes the importance of precise TMIE expression for proper mechanotransduction and hair cell function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kristina L Mitchem, Ellen Hibbard, Lisa A Beyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation of the novel gene Tmie results in sensory cell defects in the inner ear of spinner, a mouse model of human hearing loss DFNB6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/11.16.1887"}], "href": "https://doi.org/10.1093/hmg/11.16.1887"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12140191"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12140191"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kyoung In Cho, Jun-Gyo Suh, Jeong Woong Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The circling mouse (C57BL/6J-cir) has a 40-kilobase genomic deletion that includes the transmembrane inner ear (tmie) gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Comp Med (2006)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17219777"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17219777"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Seojin Park, Jeong-Han Lee, Hyun-Ju Cho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "tmie Is required for gentamicin uptake by the hair cells of mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Comp Med (2013)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23582420"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23582420"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Bo Zhao, Zizhen Wu, Nicolas Grillet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMIE is an essential component of the mechanotransduction machinery of cochlear hair cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2014.10.041"}], "href": "https://doi.org/10.1016/j.neuron.2014.10.041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25467981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25467981"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Christopher L Cunningham, Xufeng Qiu, Zizhen Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMIE Defines Pore and Gating Properties of the Mechanotransduction Channel of Mammalian Cochlear Hair Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2020.03.033"}], "href": "https://doi.org/10.1016/j.neuron.2020.03.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32343945"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32343945"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zijing Zhou, Xiaojie Yu, Biaobin Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alternative Splicing of Three Genes Encoding Mechanotransduction-Complex Proteins in Auditory Hair Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "eNeuro (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/ENEURO.0381-20.2020"}], "href": "https://doi.org/10.1523/ENEURO.0381-20.2020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33509951"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33509951"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mi Jung Shin, Jeong-Han Lee, Dong Hoon Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ectopic expression of tmie transgene induces various recovery levels of behavior and hearing ability in the circling mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2008.06.064"}], "href": "https://doi.org/10.1016/j.bbrc.2008.06.064"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18586001"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18586001"}]}]}]}