Cdk1-mediated DIAPH1 phosphorylation maintains metaphase cortical tension and inactivates the spindle assembly checkpoint at anaphase

Nature Communications
Koutarou NishimuraMakoto Nakanishi

Abstract

Animal cells undergo rapid rounding during mitosis, ensuring proper chromosome segregation, during which an outward rounding force abruptly increases upon prometaphase entry and is maintained at a constant level during metaphase. Initial cortical tension is generated by the actomyosin system to which both myosin motors and actin network architecture contribute. However, how cortical tension is maintained and its physiological significance remain unknown. We demonstrate here that Cdk1-mediated phosphorylation of DIAPH1 stably maintains cortical tension after rounding and inactivates the spindle assembly checkpoint (SAC). Cdk1 phosphorylates DIAPH1, preventing profilin1 binding to maintain cortical tension. Mutation of DIAPH1 phosphorylation sites promotes cortical F-actin accumulation, increases cortical tension, and delays anaphase onset due to SAC activation. Measurement of the intra-kinetochore length suggests that Cdk1-mediated cortex relaxation is indispensable for kinetochore stretching. We thus uncovered a previously unknown mechanism by which Cdk1 coordinates cortical tension maintenance and SAC inactivation at anaphase onset.

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Citations

Mar 19, 2020·Open Biology·Francesca RizzelliMarina Mapelli
Apr 5, 2020·Nature Communications·Isma BennabiMarie-Emilie Terret
Jan 6, 2021·Nature Communications·Cheng-Rung HuangChang-Shi Chen
Jan 22, 2022·Clinical Genetics·Bong Jik KimTakehiko Ueyama

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Methods Mentioned

BETA
immunoprecipitation
pull-down
FACS
ELISA
fluorescence recovery after photobleaching
atomic force microscopy
AFM
PCR
electrophoresis
Assay

Software Mentioned

II
Image J
NetPhosK
BZ
Bitplane

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