{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that mechanosensitive ion channels of the TMEM63 family are key mediators of diverse physiological processes. One study demonstrated that the three TMEM63 paralogues (TMEM63A, TMEM63B, and TMEM63C) must function together to form a hyperosmolarity‐activated channel that contributes to osmoreception, thereby helping maintain extracellular fluid homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n \nIn another investigation of pulmonary physiology, TMEM63A and TMEM63B were shown to reside predominantly on the limiting membrane of lamellar bodies in alveolar type 2 epithelial cells. These channels are activated by mechanical stretch during lung expansion, thereby facilitating the release of pulmonary surfactant and ATP—a process essential for initiating effective respiration at birth and for sustaining lung function throughout life."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n\nFurther work has expanded the role of TMEM63 channels to intracellular compartments. In Drosophila, the TMEM63 homologue localized to lysosomes acts as a mechanosensor, modulating lysosomal morphology and degradation. This function appears to be conserved in mammals, where TMEM63A similarly confers lysosomal mechanosensitivity and contributes to organellar function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n\nAdditionally, in the context of chronic post-amputation pain, TMEM63A is highly expressed in mechanical pain-producing nociceptors. Its upregulation in the residual nerve structures and dorsal root ganglia promotes mechanical allodynia, in part through an interaction with infiltrating macrophages that amplifies pro-inflammatory signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n\nIt is important to note that while the query refers to SNORD114-11—a small nucleolar RNA typically involved in RNA modification and processing—the provided abstracts do not address SNORD114-11. Instead, they collectively underscore the multifaceted roles of TMEM63 channels in mechanosensation across different tissues and physiological contexts.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xin Zhao, Xiaojuan Yan, Yuanhu Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Co-expression of mouse TMEM63A, TMEM63B and TMEM63C confers hyperosmolarity activated ion currents in HEK293 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biochem Funct (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cbf.3185"}], "href": "https://doi.org/10.1002/cbf.3185"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27045885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27045885"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Gui-Lan Chen, Jing-Yi Li, Xin Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanosensitive channels TMEM63A and TMEM63B mediate lung inflation-induced surfactant secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI174508"}], "href": "https://doi.org/10.1172/JCI174508"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38127458"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38127458"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kai Li, Yanmeng Guo, Yayu Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Drosophila TMEM63 and mouse TMEM63A are lysosomal mechanosensory ion channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41556-024-01353-7"}], "href": "https://doi.org/10.1038/s41556-024-01353-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38388853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38388853"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shaofeng Pu, Yiyang Wu, Fang Tong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanosensitive Ion Channel TMEM63A Gangs Up with Local Macrophages to Modulate Chronic Post-amputation Pain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Bull (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12264-022-00910-0"}], "href": "https://doi.org/10.1007/s12264-022-00910-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35821338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35821338"}]}]}]}