RZZ-Spindly and CENP-E form an integrated platform to recruit dynein to the kinetochore corona

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's 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 show that when corona assembly is prevented through MPS1 inhibition, CENP-E is absolutely required to retain RZZS at kinetochores. An RZZS phosphomimetic mutant bypasses this requirement, demonstrating the existence of a second receptor for polymeric RZZS. 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. imageRZZ-Spindly (RZZS) complex is a building block of the kinetochore corona, which promotes chromosome alignment and mitotic checkpoint signaling. New interactions identified in this study demonstrate that RZZS and CENP-E (kinesin-7) are intimately connected and reciprocally required for their own kinetochore recruitment and dynein localization to the corona.RZZS polymerization for corona expansion requires MPS1 kinase activity and an unknown kinetochore receptor.CENP-E is necessary for the kinetochore recruitment of RZZS building blocks when MPS1 and corona expansion are inhibited.CENP-E is required for the kinetochore recruitment of dynein-dynactin even when the corona expands normally.CENP-E binds to kinetochore through interactions with BUBR1 and RZZS. The kinesin-7 CENP-E is essential for the kinetochore recruitment of RZZS complex building blocks and fibrous corona expansion when RZZS polymerization is blocked by MPS1 kinase inhibition.image