State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences University of Chinese Academy of Sciences, Shanghai, China.
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
EMBO Rep. 2019 Apr;20(4). doi: 10.15252/embr.201846735. Epub 2019 Mar 4.
Mammalian epithelial cells use a pair of parental centrioles and numerous deuterosomes as platforms for efficient basal body production during multiciliogenesis. How deuterosomes form and function, however, remain controversial. They are proposed to arise either spontaneously for massive centriole biogenesis or in a daughter centriole-dependent manner as shuttles to carry away procentrioles assembled at the centriole. Here, we show that both parental centrioles are dispensable for deuterosome formation. In both mouse tracheal epithelial and ependymal cells (mTECs and mEPCs), discrete deuterosomes in the cytoplasm are initially procentriole-free. They emerge at widely dispersed positions in the cytoplasm and then enlarge, concomitant with their increased ability to form procentrioles. More importantly, deuterosomes still form efficiently in mEPCs whose daughter centriole or even both parental centrioles are eliminated through shRNA-mediated depletion or drug inhibition of Plk4, a kinase essential to centriole biogenesis in both cycling cells and multiciliated cells. Therefore, deuterosomes can be assembled autonomously to mediate centriole amplification in multiciliated cells.
哺乳动物上皮细胞在进行多纤毛发生时,利用一对亲代中心粒和许多次级中心体作为有效基底体产生的平台。然而,次级中心体如何形成和发挥作用仍存在争议。它们被认为要么自发形成大量中心粒生物发生,要么以依赖于子中心粒的穿梭方式形成,以将在中心粒上组装的前中心粒带走。在这里,我们表明亲代中心粒对于次级中心体的形成都是可有可无的。在小鼠气管上皮细胞和室管膜细胞(mTECs 和 mEPCs)中,细胞质中离散的次级中心体最初是没有前中心粒的。它们出现在细胞质中广泛分散的位置,然后增大,同时它们形成前中心粒的能力也增强。更重要的是,即使通过 shRNA 介导的 Plk4 耗竭或药物抑制消除了子中心粒甚至两个亲代中心粒,mEPCs 中的次级中心体仍能有效地形成,Plk4 是有丝分裂细胞和多纤毛细胞中中心粒生物发生所必需的激酶。因此,次级中心体可以自主组装,介导多纤毛细胞中的中心粒扩增。