Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Cells. 2022 Oct 22;11(21):3337. doi: 10.3390/cells11213337.
The midbody is an organelle that forms between the two daughter cells during cytokinesis. It co-ordinates the abscission of the nascent daughter cells and is composed of a multitude of proteins that are meticulously arranged into distinct temporal and spatial localization patterns. However, very little is known about the mechanisms that regulate the localization and function of midbody proteins. Here, we analyzed the temporal and spatial profiles of key midbody proteins during mitotic exit under normal conditions and after treatment with drugs that affect phosphorylation and proteasome-mediated degradation to decipher the impacts of post-translational modifications on midbody protein dynamics. Our results highlighted that midbody proteins show distinct spatio-temporal dynamics during mitotic exit and cytokinesis that depend on both ubiquitin-mediated proteasome degradation and phosphorylation/de-phosphorylation. They also identified two discrete classes of midbody proteins: 'transient' midbody proteins-including Anillin, Aurora B and PRC1-which rapidly accumulate at the midbody after anaphase onset and then slowly disappear, and 'stable' midbody proteins-including CIT-K, KIF14 and KIF23-which instead persist at the midbody throughout cytokinesis and also post abscission. These two classes of midbody proteins display distinct interaction networks with ubiquitylation factors, which could potentially explain their different dynamics and stability during cytokinesis.
中体是细胞分裂过程中在两个子细胞之间形成的细胞器。它协调新形成的子细胞的分离,由大量的蛋白质组成,这些蛋白质被精细地排列成不同的时间和空间定位模式。然而,关于调节中体蛋白定位和功能的机制知之甚少。在这里,我们在正常条件下和用影响磷酸化和蛋白酶体介导的降解的药物处理后分析了有丝分裂退出期间关键中体蛋白的时间和空间分布,以解析翻译后修饰对中体蛋白动力学的影响。我们的结果强调,中体蛋白在有丝分裂退出和细胞分裂过程中表现出不同的时空动力学,这取决于泛素介导的蛋白酶体降解和磷酸化/去磷酸化。它们还确定了两类离散的中体蛋白:“瞬时”中体蛋白,包括 Anillin、Aurora B 和 PRC1,在后期起始后迅速在中体上积累,然后缓慢消失,以及“稳定”中体蛋白,包括 CIT-K、KIF14 和 KIF23,它们在整个细胞分裂过程中以及在分离后仍然存在于中体上。这两类中体蛋白与泛素化因子显示出不同的相互作用网络,这可能解释了它们在细胞分裂过程中不同的动力学和稳定性。