Salas-Pino Silvia, Gallardo Paola, Barrales Ramón R, Braun Sigurd, Daga Rafael R
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-Consejo Superior de Investigaciones Científicas, Junta de Andalucia, Seville, Spain.
Department of Physiological Chemistry, Biomedical Center Munich, Ludwig-Maximilians-Universität München, Planegg-Martiensried, Germany.
J Cell Biol. 2017 Nov 6;216(11):3591-3608. doi: 10.1083/jcb.201612194. Epub 2017 Oct 3.
Kinetochores (KTs) are large multiprotein complexes that constitute the interface between centromeric chromatin and the mitotic spindle during chromosome segregation. In spite of their essential role, little is known about how centromeres and KTs are assembled and how their precise stoichiometry is regulated. In this study, we show that the nuclear pore basket component Alm1 is required to maintain both the proteasome and its anchor, Cut8, at the nuclear envelope, which in turn regulates proteostasis of certain inner KT components. Consistently, -deleted cells show increased levels of KT proteins, including CENP-C, spindle assembly checkpoint activation, and chromosome segregation defects. Our data demonstrate a novel function of the nucleoporin Alm1 in proteasome localization required for KT homeostasis.
动粒(KTs)是大型多蛋白复合物,在染色体分离过程中构成着丝粒染色质与有丝分裂纺锤体之间的界面。尽管它们起着至关重要的作用,但对于着丝粒和动粒是如何组装的以及它们精确的化学计量是如何调控的,我们却知之甚少。在这项研究中,我们发现核孔篮状组件Alm1是将蛋白酶体及其锚定蛋白Cut8维持在核膜上所必需的,而这反过来又调节某些动粒内部组件的蛋白质稳态。一致地,缺失Alm1的细胞显示出动粒蛋白水平升高,包括CENP-C、纺锤体组装检查点激活以及染色体分离缺陷。我们的数据证明了核孔蛋白Alm1在动粒稳态所需的蛋白酶体定位中的新功能。