Polo regulates Spindly to prevent premature stabilization of kinetochore-microtubule attachments

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

Barbosa, J (Autor) Outra; Martins, T (Autor) Outra; Bange, T (Autor) Outra; Tao, L (Autor) Outra; Conde, C (Autor) Outra; Sunkel, CE (Autor) ICBAS

Revista

Título: EMBO Journal

ISSN: 0261-4189

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 1 Citação

Scopus - 2 Citações

Outras Informações

ID Authenticus: P-00R-H66

DOI: 10.15252/embj.2018100789

Abstract (EN): Accurate chromosome segregation in mitosis requires sister kinetochores to bind to microtubules from opposite spindle poles. The stability of kinetochore-microtubule attachments is fine-tuned to prevent or correct erroneous attachments while preserving amphitelic interactions. Polo kinase has been implicated in both stabilizing and destabilizing kinetochore-microtubule attachments. However, the mechanism underlying Polo-destabilizing activity remains elusive. Here, resorting to an RNAi screen in Drosophila for suppressors of a constitutively active Polo mutant, we identified a strong genetic interaction between Polo and the Rod-ZW10-Zwilch (RZZ) complex, whose kinetochore accumulation has been shown to antagonize microtubule stability. We find that Polo phosphorylates Spindly and impairs its ability to bind to Zwilch. This precludes dynein-mediated removal of the RZZ from kinetochores and consequently delays the formation of stable end-on attachments. We propose that high Polo-kinase activity following mitotic entry directs the RZZ complex to minimize premature stabilization of erroneous attachments, whereas a decrease in active Polo in later mitotic stages allows the formation of stable amphitelic spindle attachments. Our findings demonstrate that Polo tightly regulates the RZZ-Spindly-dynein module during mitosis to ensure the fidelity of chromosome segregation.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 22