Kim Seongjae, Chien Yuan-Hung, Ryan Amy, Kintner Chris
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Hastings Center for Pulmonary Research, Department of Medicine, University of Southern California, Los Angeles, CA, USA.
Sci Adv. 2022 Apr;8(13):eabm7538. doi: 10.1126/sciadv.abm7538. Epub 2022 Apr 1.
Massive centriole amplification during multiciliated cell (MCC) differentiation is a notable example of organelle biogenesis. This process is thought to be enabled by a derived cell cycle state, but the key cell cycle components required for centriole amplification in MCC progenitors remain poorly defined. Here, we show that () expression is up-regulated and acts in MCC progenitors after cell cycle exit to transiently inhibit anaphase-promoting complex/cyclosome (APC/C) activity. We find that this inhibition is required for the phosphorylation and activation of a key cell cycle kinase, plk1, which acts, in turn, to promote different steps required for centriole amplification and basal body formation, including centriole disengagement, apical migration, and maturation into basal bodies. This emi2-APC/C-plk1 axis is also required to down-regulate gene expression essential for centriole amplification after differentiation is complete. These results identify an emi2-APC/C-plk1 axis that promotes and then terminates centriole assembly and basal body formation during MCC differentiation.
多纤毛细胞（MCC）分化过程中大量中心粒扩增是细胞器生物发生的一个显著例子。这个过程被认为是由一种衍生的细胞周期状态所促成的，但MCC祖细胞中中心粒扩增所需的关键细胞周期成分仍不清楚。在这里，我们表明（）的表达上调，并在细胞周期退出后在MCC祖细胞中发挥作用，以短暂抑制后期促进复合物/细胞周期体（APC/C）的活性。我们发现这种抑制对于关键细胞周期激酶plk1的磷酸化和激活是必需的，而plk1反过来又促进中心粒扩增和基体形成所需的不同步骤，包括中心粒脱离、顶端迁移以及成熟为基体。这个emi2-APC/C-plk1轴在分化完成后对于下调中心粒扩增所必需的基因表达也是必需的。这些结果确定了一个emi2-APC/C-plk1轴，它在MCC分化过程中促进并随后终止中心粒组装和基体形成。
