Abstract：
The transmembrane 63 (TMEM63) family of proteins are originally identified as homologs of the osmosensitive calcium-permeable (OSCA) channels in plants. Mechanosensitivity of OSCA and TMEM63 proteins are recently demonstrated in addition to their proposed activation mechanism by hyper/hypo-osmolarity. TMEM63 proteins exist in all animals, with a single member in Drosophila (TMEM63) and three members in mammals (TMEM63 A/B/C). In humans, monoallelic variants of TMEM63A have been reported to cause transient hypomyelination during infancy, or severe hypomyelination and global developmental delay. Heterozygous variants of TMEM63B are found in patients with intellectual disability and abnormal motor function and brain morphology. Biallelic variants of TMEM63C are associated with hereditary spastic paraplegias accompanied by mild or no intellectual disability. Physiological functions of TMEM63 proteins clearly recognized so far include detecting food grittiness and environmental humidity in Drosophila, and supporting hearing in mice by regulating survival of cochlear hair cells. In this review, we summarize current knowledge about the activation mechanisms and biological functions of TMEM63 channels, and provide a concise reference for researchers interested in investigating more physiological and pathogenic roles of this family of proteins with ubiquitous expression in the body.
摘要：
蛋白质的跨膜63（TMEM63）家族最初被鉴定为植物中渗透敏感性钙可渗透（OSCA）通道的同源物。除了通过高/低渗透压提出的激活机制外，最近还证明了OSCA和TMEM63蛋白的机械敏感性。TMEM63蛋白存在于所有动物中，果蝇中只有一个成员（TMEM63），哺乳动物中有三个成员（TMEM63A/B/C）。在人类中,据报道，TMEM63A的单等位基因变异体在婴儿期会导致短暂的髓鞘减少，或严重的骨髓溶解不足和整体发育迟缓。TMEM63B的杂合变体在患有智力障碍和运动功能和脑形态异常的患者中发现。TMEM63C的双等位基因变异体与伴有轻度或无智力障碍的遗传性痉挛性截瘫相关。到目前为止，已明确认可的TMEM63蛋白的生理功能包括检测果蝇中的食物沙质和环境湿度，通过调节耳蜗毛细胞的存活来支持小鼠的听力。在这次审查中,我们总结了有关TMEM63通道的激活机制和生物学功能的最新知识，并为有兴趣研究该蛋白质家族在体内普遍存在的更多生理和致病作用的研究人员提供了简明的参考。
