2024年11月,中国科学院分子细胞科学研究中心,上海生物化学与细胞生物学研究所多细胞系统重点实验室,上海工业大学生命科学与技术学院,中国科学院大学,中国科学院生物物理研究所生物成像中心,上海交通大学医学院新华医院早期生命健康研究所,上海市儿童环境健康教育部重点实验室,中国科学院大学杭州高等研究院生命科学学院,浙江省系统健康科学重点实验室(Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China. School of Life Science and Technology, ShanghaiTech University, Shanghai, China.University of Chinese Academy of Sciences, Beijing, China.Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.Ministry of EducationShanghai Key Laboratory of Children’s Environmental Health, Institute of Early Life Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
These authors contributed equally: Xinwen Pan, Chuyu Fang, Chuan Shen.) Xinwen Pan老师研究团队在《Nature Communications》上发表论文:
“Directional ciliary beats across epithelia require Ccdc57-mediated coupling between axonemal orientation and basal body polarity"
“通过上皮的定向纤毛搏动需要ccdc57介导的轴突取向和基体极性之间的耦合"
Abstract:
Motile cilia unify their axonemal orientations (AOs), or beat directions, across epithelia to drive liquid flows. This planar polarity results from cytoskeleton-driven swiveling of basal foot (BF), a basal body (BB) appendage coincident with the AO, in response to regulatory cues. How and when the BF-AO relationship is established, however, are unaddressed. Here, we show that the BF-AO coupling occurs during rotational polarizations of BBs and requires Ccdc57. Ccdc57 localizes on BBs as a rotationally-asymmetric punctum, which polarizes away from the BF in BBs having achieved the rotational polarity to probably fix the BF-AO relationship. Consistently, Ccdc57-deficient ependymal multicilia lack the BF-AO coupling and display directional beats at only single cell level. Ccdc57 −/− tracheal multicilia also fail to fully align their BFs. Furthermore, Ccdc57 −/− mice manifest severe hydrocephalus, due to impaired cerebrospinal fluid flow, and high mortality. These findings unravel mechanisms governing the planar polarity of epithelial motile cilia.
摘要:
运动纤毛统一其轴突方向(AOs),或拍打方向,跨越上皮驱动液体流动。这种平面极性是由细胞骨架驱动的基底足(BF)的旋转引起的,基底足(BB)是与AO一致的附属物,是对调节信号的响应。然而,如何以及何时建立BF-AO关系尚未得到解决。在这里,我们证明了BF-AO耦合发生在BBs的旋转极化过程中,并且需要Ccdc57。Ccdc57在BBs上定位为一个旋转不对称的点,它在BBs中远离BF极化,实现了旋转极性,可能是为了固定BF- ao关系。同样,ccdc57缺陷的室管膜多毛缺乏BF-AO耦合,仅在单细胞水平上显示定向搏动。Ccdc57 - / -气管多毛也不能对准它们的BFs。此外,由于脑脊液流动受损,Ccdc57 - / -小鼠表现出严重的脑积水和高死亡率。这些发现揭示了控制上皮运动纤毛平面极性的机制。
该论文中,hAMSCs的体外培养是使用Ausbian特级胎牛血清完成的。