Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK
J Cell Sci. 2021 Jan 8;134(1):jcs251025. doi: 10.1242/jcs.251025.
Errors in mitotic chromosome segregation can lead to DNA damage and aneuploidy, both hallmarks of cancer. To achieve synchronous error-free segregation, mitotic chromosomes must align at the metaphase plate with stable amphitelic attachments to microtubules emanating from opposing spindle poles. The astrin-kinastrin (astrin is also known as SPAG5 and kinastrin as SKAP) complex, also containing DYNLL1 and MYCBP, is a spindle and kinetochore protein complex with important roles in bipolar spindle formation, chromosome alignment and microtubule-kinetochore attachment. However, the molecular mechanisms by which astrin-kinastrin fulfils these diverse roles are not fully understood. Here, we characterise a direct interaction between astrin and the mitotic kinase Plk1. We identify the Plk1-binding site on astrin as well as four Plk1 phosphorylation sites on astrin. Regulation of astrin by Plk1 is dispensable for bipolar spindle formation and bulk chromosome congression, but promotes stable microtubule-kinetochore attachments and metaphase plate maintenance. It is known that Plk1 activity is required for effective microtubule-kinetochore attachment formation, and we suggest that astrin phosphorylation by Plk1 contributes to this process.
有丝分裂染色体分离错误可导致 DNA 损伤和非整倍体，这两者都是癌症的标志。为了实现无差错的同步分离，有丝分裂染色体必须与来自对侧纺锤体极的微管稳定的双联体附着在中期板上对齐。astrin-kinastrin（astrin 也称为 SPAG5，kinastrin 称为 SKAP）复合物，还包含 DYNLL1 和 MYCBP，是一种纺锤体和动粒蛋白复合物，在双极纺锤体形成、染色体排列和微管-动粒附着中具有重要作用。然而，astrin-kinastrin 发挥这些不同作用的分子机制尚不完全清楚。在这里，我们描述了 astrin 与有丝分裂激酶 Plk1 之间的直接相互作用。我们确定了 astrin 上的 Plk1 结合位点以及 astrin 上的四个 Plk1 磷酸化位点。Plk1 对 astrin 的调节对于双极纺锤体的形成和大量染色体的汇聚是可有可无的，但它促进了稳定的微管-动粒附着和中期板的维持。众所周知，Plk1 的活性对于有效的微管-动粒附着形成是必需的，我们认为 Plk1 对 astrin 的磷酸化有助于这一过程。
