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

EMBO J. 2023 Dec 11;42(24):e114838. doi: 10.15252/embj.2023114838. Epub 2023 Nov 20.

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'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.

Keywords: CENP-E; centromere; kinetochore fibrous corona; mitosis; spindle assembly checkpoint.

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromosome Segregation
  • Dynactin Complex / genetics
  • Dyneins* / genetics
  • Dyneins* / metabolism
  • Kinesins / genetics
  • Kinetochores* / metabolism
  • Microtubules / metabolism
  • Mitosis
  • Spindle Apparatus / metabolism

Substances

  • Dyneins
  • Kinesins
  • Cell Cycle Proteins
  • Dynactin Complex