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bioRxiv · 10.1101/2023.04.25.538277

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

Cmentowski, V.·D'Amico, E.·Ciossani, G.·Wohlgemuth, S.·Owa, M.·Dynlacht, B. D.·Musacchio, A.
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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 coronas 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.

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Cmentowski, V., D'Amico, E., Ciossani, G., Wohlgemuth, S., Owa, M., Dynlacht, B. D., Musacchio, A.. 2023-04-25. A mechanism that integrates microtubule motors of opposite polarity at the kinetochore corona. https://doi.org/10.1101/2023.04.25.538277

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