Feedback control of PLK1 by Apolo1 ensures accurate chromosome segregation

Leilei Xu; Mahboob Ali; Wenxiu Duan; Xiao Yuan; Fatima Garba; McKay Mullen; Binwen Sun; Ina Poser; Hequan Duan; Jianlin Lu; Ruijun Tian; Yushu Ge; Lingluo Chu; Weijun Pan; Dongmei Wang; Anthony Hyman; Hadiyah Green; Lin Li; Zhen Dou; Dan Liu; Xing Liu; Xuebiao Yao

doi:10.1016/j.celrep.2021.109343

Feedback control of PLK1 by Apolo1 ensures accurate chromosome segregation

Cell Rep. 2021 Jul 13;36(2):109343. doi: 10.1016/j.celrep.2021.109343.

Authors

Leilei Xu¹, Mahboob Ali², Wenxiu Duan³, Xiao Yuan⁴, Fatima Garba⁵, McKay Mullen¹, Binwen Sun⁶, Ina Poser⁷, Hequan Duan⁸, Jianlin Lu², Ruijun Tian⁹, Yushu Ge³, Lingluo Chu¹, Weijun Pan¹⁰, Dongmei Wang², Anthony Hyman⁷, Hadiyah Green⁵, Lin Li¹⁰, Zhen Dou¹¹, Dan Liu¹², Xing Liu¹³, Xuebiao Yao¹⁴

Affiliations

¹ MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Hefei 230027, China; Keck Center for Molecular Imaging, Morehouse School of Medicine, Atlanta, GA 30310, USA.
² MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Hefei 230027, China.
³ Anhui Key Laboratory for Chemical Biology, Hefei National Center for Physical Sciences at Microscale, Hefei 230027, China.
⁴ MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Hefei 230027, China; Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address: yuanxiao@ustc.edu.cn.
⁵ Keck Center for Molecular Imaging, Morehouse School of Medicine, Atlanta, GA 30310, USA.
⁶ National Chromatographic Research and Analysis Center, Dalian 116023, China.
⁷ Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
⁸ MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Hefei 230027, China; Keck Center for Molecular Imaging, Morehouse School of Medicine, Atlanta, GA 30310, USA; Anhui Key Laboratory for Chemical Biology, Hefei National Center for Physical Sciences at Microscale, Hefei 230027, China.
⁹ Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China.
¹⁰ Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
¹¹ MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Hefei 230027, China; Anhui Key Laboratory for Chemical Biology, Hefei National Center for Physical Sciences at Microscale, Hefei 230027, China. Electronic address: douzhen@ustc.edu.cn.
¹² Anhui Key Laboratory for Chemical Biology, Hefei National Center for Physical Sciences at Microscale, Hefei 230027, China. Electronic address: dliu919@ustc.edu.cn.
¹³ MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Hefei 230027, China; Keck Center for Molecular Imaging, Morehouse School of Medicine, Atlanta, GA 30310, USA. Electronic address: xing1017@ustc.edu.cn.
¹⁴ MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Hefei 230027, China; Keck Center for Molecular Imaging, Morehouse School of Medicine, Atlanta, GA 30310, USA. Electronic address: yaoxb@ustc.edu.cn.

Abstract

Stable transmission of genetic material during cell division requires accurate chromosome segregation. PLK1 dynamics at kinetochores control establishment of correct kinetochore-microtubule attachments and subsequent silencing of the spindle checkpoint. However, the regulatory mechanism responsible for PLK1 activity in prometaphase has not yet been affirmatively identified. Here we identify Apolo1, which tunes PLK1 activity for accurate kinetochore-microtubule attachments. Apolo1 localizes to kinetochores during early mitosis, and suppression of Apolo1 results in misaligned chromosomes. Using the fluorescence resonance energy transfer (FRET)-based PLK1 activity reporter, we found that Apolo1 sustains PLK1 kinase activity at kinetochores for accurate attachment during prometaphase. Apolo1 is a cognate substrate of PLK1, and the phosphorylation enables PP1γ to inactivate PLK1 by dephosphorylation. Mechanistically, Apolo1 constitutes a bridge between kinase and phosphatase, which governs PLK1 activity in prometaphase. These findings define a previously uncharacterized feedback loop by which Apolo1 provides fine-tuning for PLK1 to guide chromosome segregation in mitosis.

Keywords: Apolo1; PLK1; PP1γ; chromosome segregation; kinetochore; mitosis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Motifs
Amino Acid Sequence
Cell Cycle Proteins / metabolism*
Chromosome Segregation*
Feedback, Physiological*
HEK293 Cells
HeLa Cells
Humans
Kinetochores / metabolism
Mitosis
Phosphoprotein Phosphatases / metabolism
Phosphorylation
Phosphoserine / metabolism
Polo-Like Kinase 1
Protein Binding
Protein Serine-Threonine Kinases / metabolism*
Proteins / chemistry
Proteins / metabolism*
Proto-Oncogene Proteins / metabolism*

Substances

Cell Cycle Proteins
Proteins
Proto-Oncogene Proteins
Phosphoserine
Protein Serine-Threonine Kinases
Phosphoprotein Phosphatases

Abstract

Publication types

MeSH terms

Substances

Grants and funding