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定向纤毛拍打 across 上皮需要 Ccdc57 介导的轴丝取向和基体极性之间的耦合。

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

机构信息

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.

出版信息

Nat Commun. 2024 Nov 26;15(1):10249. doi: 10.1038/s41467-024-54766-1.

DOI:10.1038/s41467-024-54766-1
PMID:39592607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11599927/
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

纤毛的轴丝取向（AO）或摆动方向在细胞间是统一的，从而推动液体流动。这种平面极性是由细胞骨架驱动的基底脚（BF）的旋转引起的，BF 是与 AO 一致的基底体（BB）附属物，这是对调节信号的反应。然而，BF-AO 关系是如何以及何时建立的，目前尚未得到解决。在这里，我们表明 BF-AO 偶联发生在 BB 的旋转极化过程中，需要 Ccdc57。Ccdc57 作为一个旋转不对称的点状结构定位于 BB 上，在 BB 实现旋转极性时，该点状结构从 BF 处移开，可能会固定 BF-AO 关系。一致地，Ccdc57 缺陷的室管膜多纤毛缺乏 BF-AO 偶联，并且仅在单个细胞水平显示定向摆动。Ccdc57 缺陷的气管多纤毛也不能完全对齐它们的 BF。此外，Ccdc57 缺陷的小鼠表现出严重的脑积水，这是由于脑脊液流动受损和高死亡率所致。这些发现揭示了控制上皮运动纤毛平面极性的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/18d6dcadb75f/41467_2024_54766_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/a10de162f29c/41467_2024_54766_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/30f035922237/41467_2024_54766_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/79bdd224e6a3/41467_2024_54766_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/0130b8920e0b/41467_2024_54766_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/f42c18b8f903/41467_2024_54766_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/766721d41873/41467_2024_54766_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/574a76a242ff/41467_2024_54766_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/18d6dcadb75f/41467_2024_54766_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/a10de162f29c/41467_2024_54766_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/30f035922237/41467_2024_54766_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/79bdd224e6a3/41467_2024_54766_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/0130b8920e0b/41467_2024_54766_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/f42c18b8f903/41467_2024_54766_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/766721d41873/41467_2024_54766_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/574a76a242ff/41467_2024_54766_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58f1/11599927/18d6dcadb75f/41467_2024_54766_Fig8_HTML.jpg

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本文引用的文献

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J Cell Biol. 2024 Jan 1;223(1). doi: 10.1083/jcb.202307150. Epub 2023 Nov 30.
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Ccdc57 is required for straightening the body axis by regulating ciliary motility in the brain ventricle of zebrafish.
Ccdc57 通过调节斑马鱼脑室中的纤毛运动来矫正身体轴。
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