Faithful chromosome segregation relies on the ability of the spindle assembly checkpoint (SAC) to delay anaphase onset until chromosomes are attached to the mitotic spindle via their kinetochores. MPS1 kinase is recruited to kinetochores to initiate SAC signaling and is removed from kinetochores once stable microtubule attachments have been formed to allow normal mitotic progression. Here, we show that a helical fragment within the kinetochore-targeting N-terminal extension (NTE) module of MPS1 is required for interactions with kinetochores and forms intramolecular interactions with its adjacent tetratricopeptide repeat (TPR) domain. Bypassing this NTE-TPR interaction results in high MPS1 levels at kinetochores due to loss of regulatory input into MPS1 localization, inefficient MPS1 delocalization upon microtubule attachment, and SAC silencing defects. These results show that SAC responsiveness to attachments relies on regulated intramolecular interactions in MPS1 and highlight the sensitivity of mitosis to perturbations in the dynamics of the MPS1-NDC80-C interactions.
Pubmed ID: 30784592 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Astrin/MAP126
View all literature mentionsThis monoclonal targets Mps1 NT clone 3-472-1
View all literature mentionsThis monoclonal targets HEC1
View all literature mentionsThis unknown targets anti-CENP-C
View all literature mentionsThis monoclonal targets α-tubulin
View all literature mentions