Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education and State, Key Laboratory of Bio-membrane and Membrane Bio-engineering, College of Life Sciences, Peking University, Beijing 100871, China.
Cell Rep. 2013 Sep 26;4(6):1100-7. doi: 10.1016/j.celrep.2013.08.005. Epub 2013 Sep 12.
During interphase, centrosomes are connected by a proteinaceous linker between the proximal ends of the centrioles, which is important for the centrosomes to function as a single microtubule-organizing center. However, the composition and regulation of centrosomal linker remain largely unknown. Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. Moreover, LRRC45 interacts with both C-Nap1 and rootletin and is phosphorylated by Nek2A at S661 during mitosis. After phosphorylation, both LRRC45 centrosomal localization and fiber-like structures are significantly reduced, which subsequently leads to centrosome separation. Thus, LRRC45 is a critical component of the proteinaceous linker between two centrioles and is required for centrosome cohesion.
在有丝分裂间期,中心体通过中心粒近端之间的蛋白质连接体连接在一起,这对于中心体作为一个微管组织中心发挥功能非常重要。然而,中心体连接体的组成和调节在很大程度上仍然未知。在这里,我们表明 LRRC45 是一种中心体连接体,它定位于中心粒的近端,并在它们之间形成纤维状结构。LRRC45 的耗竭导致有丝分裂间期中心体分裂。此外,LRRC45 与 C-Nap1 和根蛋白相互作用,并在有丝分裂期间被 Nek2A 在 S661 处磷酸化。磷酸化后,LRRC45 的中心体定位和纤维状结构显著减少,随后导致中心体分离。因此,LRRC45 是两个中心粒之间蛋白质连接体的关键组成部分,对于中心体的凝聚是必需的。