Drosophila Polo regulates the spindle assembly checkpoint through Mps1-dependent BubR1 phosphorylation

• Published in: The EMBO journal Vol. 32; no. 12; pp. 1761 - 1777
• Main Authors: Conde, Carlos, Osswald, Mariana, Barbosa, João, Moutinho-Santos, Tatiana, Pinheiro, Diana, Guimarães, Sofia, Matos, Irina, Maiato, Helder, Sunkel, Claudio E
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 12.06.2013; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Animals; Aurora Kinases; BubR1 phosphorylation; Cdc20 Proteins; Cdc20-BubR1 complex; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell division; Cell Line; Chromosomes; Drosophila melanogaster; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Eukaryotes; Genomics; Insects; Kinetochores - metabolism; Mps1; Phosphorylation; Phosphorylation - physiology; Polo; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; SAC; Spindle Apparatus - genetics; Spindle Apparatus - metabolism
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2013.109

Maintenance of genomic stability during eukaryotic cell division relies on the spindle assembly checkpoint (SAC) that prevents mitotic exit until all chromosomes are properly attached to the spindle. Polo is a mitotic kinase proposed to be involved in SAC function, but its role has remained elusive. We demonstrate that Polo and Aurora B functional interdependency comprises a positive feedback loop that promotes Mps1 kinetochore localization and activity. Expression of constitutively active Polo restores normal Mps1 kinetochore levels even after Aurora B inhibition, highlighting a role for Polo in Mps1 recruitment to unattached kinetochores downstream of Aurora B. We also show that Mps1 kinetochore localization is required for BubR1 hyperphosphorylation and formation of the 3F3/2 phosphoepitope. This is essential to allow recruitment of Cdc20 to unattached kinetochores and the assembly of anaphase‐promoting complex/cyclosome‐inhibitory complexes to levels that ensure long‐term SAC activity. We propose a model in which Polo controls Mps1‐dependent BubR1 phosphorylation to promote Cdc20 kinetochore recruitment and sustained SAC function. Dissection of the interplay between mitotic checkpoint kinases in flies reveals a key role for Polo kinase in Mps1 kinetochore recruitment, demonstrating the adaptive plasticity of metazoan spindle assembly checkpoint signalling.