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RZZ-Spindly and CENP-E form an integrated platform to recruit dynein to the kinetochore corona.
Cmentowski, Verena; Ciossani, Giuseppe; d'Amico, Ennio; Wohlgemuth, Sabine; Owa, Mikito; Dynlacht, Brian; Musacchio, Andrea.
Afiliação
  • Cmentowski V; Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
  • Ciossani G; Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Essen, Germany.
  • d'Amico E; Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
  • Wohlgemuth S; Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
  • Owa M; Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
  • Dynlacht B; Department of Pathology, New York University Cancer Institute, New York University School of Medicine, New York, NY, USA.
  • Musacchio A; Department of Pathology, New York University Cancer Institute, New York University School of Medicine, New York, NY, USA.
EMBO J ; 42(24): e114838, 2023 Dec 11.
Article em En | MEDLINE | ID: mdl-37984321
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dineínas / Cinetocoros Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dineínas / Cinetocoros Idioma: En Ano de publicação: 2023 Tipo de documento: Article