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纤毛数量在多纤毛细胞中的调控。

Regulation of cilia abundance in multiciliated cells.

机构信息

Nephrology Division, Department of Medicine, Washington University, St Louis, United States.

Center for Cancer Research, National Cancer Institute, Frederick, United States.

出版信息

Elife. 2019 Apr 26;8:e44039. doi: 10.7554/eLife.44039.

Abstract

Multiciliated cells (MCC) contain hundreds of motile cilia used to propel fluid over their surface. To template these cilia, each MCC produces between 100-600 centrioles by a process termed centriole amplification. Yet, how MCC regulate the precise number of centrioles and cilia remains unknown. Airway progenitor cells contain two parental centrioles (PC) and form structures called deuterosomes that nucleate centrioles during amplification. Using an ex vivo airway culture model, we show that ablation of PC does not perturb deuterosome formation and centriole amplification. In contrast, loss of PC caused an increase in deuterosome and centriole abundance, highlighting the presence of a compensatory mechanism. Quantification of centriole abundance in vitro and in vivo identified a linear relationship between surface area and centriole number. By manipulating cell size, we discovered that centriole number scales with surface area. Our results demonstrate that a cell-intrinsic surface area-dependent mechanism controls centriole and cilia abundance in multiciliated cells.

摘要

纤毛细胞(MCC)含有数百个用于推动其表面流体的运动纤毛。为了模板这些纤毛,每个 MCC 通过称为中心体扩增的过程产生 100-600 个中心体。然而,MCC 如何调节精确的中心体和纤毛数量仍然未知。气道祖细胞包含两个亲本中心体(PC),并形成称为二联体的结构,在扩增过程中核化中心体。使用体外气道培养模型,我们表明 PC 的消融不会破坏二联体的形成和中心体的扩增。相比之下,PC 的丢失导致二联体和中心体丰度增加,突出了存在补偿机制。体外和体内的中心体丰度定量分析表明,表面积与中心体数量之间存在线性关系。通过操纵细胞大小,我们发现中心体数量与表面积成比例。我们的结果表明,细胞内在的表面积依赖机制控制着纤毛细胞中中心体和纤毛的丰度。

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