通過上皮的定向纖毛搏動需要ccdc57介導的軸突取向和基體極性之間的耦合

2024年11月，中國科學院分子細胞科學研究中心，上海生物化學與細胞生物學研究所多細胞系統重點實驗室，上海工業大學生命科學與技術學院，中國科學院大學，中國科學院生物物理研究所生物成像中心，上海交通大學醫學院新華醫院早期生命健康研究所，上海市兒童環境健康教育部重點實驗室，中國科學院大學杭州高等研究院生命科學學院，浙江省系統健康科學重點實驗室(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老師研究團隊在《Nature Communications》上發表論文：

“Directional ciliary beats across epithelia require Ccdc57-mediated coupling between axonemal orientation and basal body polarity"

“通過上皮的定向纖毛搏動需要ccdc57介導的軸突取向和基體極性之間的耦合"

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：

運動纖毛統一其軸突方向（AOs），或拍打方向，跨越上皮驅動液體流動。這種平面極性是由細胞骨架驅動的基底足（BF）的旋轉引起的，基底足（BB）是與AO一致的附屬物，是對調節信號的響應。然而，如何以及何時建立BF-AO關系尚未得到解決。在這里，我們證明了BF-AO耦合發生在BBs的旋轉極化過程中，并且需要Ccdc57。Ccdc57在BBs上定位為一個旋轉不對稱的點，它在BBs中遠離BF極化，實現了旋轉極性，可能是為了固定BF- ao關系。同樣，ccdc57缺陷的室管膜多毛缺乏BF-AO耦合，僅在單細胞水平上顯示定向搏動。Ccdc57 - / -氣管多毛也不能對準它們的BFs。此外，由于腦脊液流動受損，Ccdc57 - / -小鼠表現出嚴重的腦積水和高死亡率。這些發現揭示了控制上皮運動纖毛平面極性的機制。

該論文中，hAMSCs的體外培養是使用Ausbian特級胎牛血清完成的。