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机械拉伸通过 Piezo1 在多纤毛细胞中按中心体数量对顶区进行缩放。

Mechanical stretch scales centriole number to apical area via Piezo1 in multiciliated cells.

机构信息

Pediatric Genomics Discovery Program, Department of Pediatrics and Genetics, Yale University School of Medicine, New Haven, United States.

Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, United States.

出版信息

Elife. 2021 Jun 29;10:e66076. doi: 10.7554/eLife.66076.

Abstract

How cells count and regulate organelle number is a fundamental question in cell biology. For example, most cells restrict centrioles to two in number and assemble one cilium; however, multiciliated cells (MCCs) synthesize hundreds of centrioles to assemble multiple cilia. Aberration in centriole/cilia number impairs MCC function and can lead to pathological outcomes. Yet how MCCs control centriole number remains unknown. Using , we demonstrate that centriole number scales with apical area over a remarkable 40-fold change in size. We find that tensile forces that shape the apical area also trigger centriole amplification based on both cell stretching experiments and disruption of embryonic elongation. Unexpectedly, Piezo1, a mechanosensitive ion channel, localizes near each centriole suggesting a potential role in centriole amplification. Indeed, depletion of Piezo1 affects centriole amplification and disrupts its correlation with the apical area in a tension-dependent manner. Thus, mechanical forces calibrate cilia/centriole number to the MCC apical area via Piezo1. Our results provide new perspectives to study organelle number control essential for optimal cell function.

摘要

细胞如何计数和调节细胞器数量是细胞生物学的一个基本问题。例如,大多数细胞将中心体限制为两个,并组装一个纤毛;然而,多纤毛细胞 (MCCs) 合成数百个中心体以组装多个纤毛。中心体/纤毛数量的异常会损害 MCC 的功能,并导致病理性后果。然而,MCC 如何控制中心体数量仍然未知。使用 ,我们证明中心体数量与顶区面积成比例,在大小上有显著的 40 倍变化。我们发现,塑造顶区的张力也会触发基于细胞拉伸实验和胚胎伸长破坏的中心体扩增。出乎意料的是,Piezo1,一种机械敏感的离子通道,位于每个中心体附近,表明其在中心体扩增中可能具有潜在作用。事实上,Piezo1 的耗竭会影响中心体扩增,并以张力依赖的方式破坏其与顶区的相关性。因此,机械力通过 Piezo1 将纤毛/中心体数量校准到 MCC 顶区。我们的结果为研究细胞器数量控制提供了新的视角,这对于优化细胞功能至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72a7/8270640/cac75bc53282/elife-66076-fig1.jpg

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