MPS1 localizes to microtubule-attached kinetochores and actively promotesmicrotubule release

SummaryIn eukaryotes, the spindle assembly checkpoint protects genome stability in mitosis by preventing anaphase onset until incorrect microtubule-kinetochore attachment geometries have been eliminated and chromosome biorientation has been completed. These error correction and checkpoint processes are linked by two conserved serine/threonine kinases, Aurora B and MPS1 1, 2. In the prevailing model for spindle checkpoint signaling, MPS1 detects microtubule-free kinetochores generated by the Aurora B-dependent error correction pathway, and initiates spindle checkpoint signaling. However, we find that MPS1 initially localizes to microtubule-attached kinetochores in a manner dependent on the relative activities of Aurora B and its counteracting phosphatase PP2A-B56, and then actively promotes microtubule release. Thus, MPS1 is not a passive sensor for the microtubule binding state of kinetochores but actively generates microtubule-free checkpoint signaling kinetochores. MPS1 is thus instrumental for both the initial resolution of incorrect microtubule-kinetochore attachments and the downstream propagation of spindle checkpoint signaling.