Cell Reports (Jul 2021)
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
Affiliations
- Leilei Xu
- 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
- Mahboob Ali
- MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Hefei 230027, China
- Wenxiu Duan
- Anhui Key Laboratory for Chemical Biology, Hefei National Center for Physical Sciences at Microscale, Hefei 230027, China
- Xiao Yuan
- 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; Corresponding author
- Fatima Garba
- Keck Center for Molecular Imaging, Morehouse School of Medicine, Atlanta, GA 30310, USA
- McKay Mullen
- 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
- Binwen Sun
- National Chromatographic Research and Analysis Center, Dalian 116023, China
- Ina Poser
- Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany
- Hequan Duan
- 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
- Jianlin Lu
- MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Hefei 230027, China
- Ruijun Tian
- Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China
- Yushu Ge
- Anhui Key Laboratory for Chemical Biology, Hefei National Center for Physical Sciences at Microscale, Hefei 230027, China
- Lingluo Chu
- 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
- Weijun Pan
- Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China
- Dongmei Wang
- MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China, Hefei 230027, China
- Anthony Hyman
- Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany
- Hadiyah Green
- Keck Center for Molecular Imaging, Morehouse School of Medicine, Atlanta, GA 30310, USA
- Lin Li
- Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China
- Zhen Dou
- 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; Corresponding author
- Dan Liu
- Anhui Key Laboratory for Chemical Biology, Hefei National Center for Physical Sciences at Microscale, Hefei 230027, China; Corresponding author
- Xing Liu
- 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; Corresponding author
- Xuebiao Yao
- 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; Corresponding author
- Journal volume & issue
-
Vol. 36,
no. 2
p. 109343
Abstract
Summary: 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.
