RZZ-Spindly and CENP-E Form an Integrated Platform to Recruit Dynein to the Kinetochore Corona

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2023 Nov 20

PMID 37984321

Authors

Verena Cmentowski

Giuseppe Ciossani

Ennio dAmico

Sabine Wohlgemuth

Mikito Owa

Brian Dynlacht

Andrea Musacchio

Affiliations

Soon will be listed here.

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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