A mechanism that integrates microtubule motors of opposite polarity at the kinetochore corona

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.25.538277v1?rss=1 Authors: Cmentowski, V., D'Amico, E., Ciossani, G., Wohlgemuth, S., Owa, M., Dynlacht, B. D., Musacchio, A. Abstract: Chromosome biorientation on the mitotic spindle is prerequisite to errorless genome inheritance. CENP-E (kinesin 7) and Dynein-Dynactin (DD), microtubule motors with opposite polarity, promote biorientation from the kinetochore corona, a polymeric structure whose assembly requires MPS1 kinase. The corona building block consists of ROD, Zwilch, ZW10, and the DD adaptor Spindly (RZZS). How CENP-E and DD are scaffolded and mutually coordinated in the corona remains unclear. Here, we report near-complete depletion of RZZS and DD from kinetochores after depletion of CENP-E and the outer kinetochore protein KNL1. With inhibited MPS1, CENP-E, which we show binds directly to RZZS, is required to retain kinetochore RZZS. An RZZS phosphomimetic mutant bypasses this requirement. With active MPS1, CENP-E is dispensable for corona expansion, but strictly required for physiological kinetochore accumulation of DD. Thus, we identify the corona as an integrated scaffold where CENP-E kinesin controls DD kinetochore loading for coordinated bidirectional transport of chromosome cargo. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC