1. Cell Biology
  2. Chromosomes and Gene Expression

The human Ska complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores

  1. Sushama Sivakumar
  2. Paweł Ł Janczyk
  3. Qianhui Qu
  4. Chad A Brautigam
  5. P Todd Stukenberg
  6. Hongtao Yu
  7. Gary J Gorbsky  Is a corresponding author
  1. Oklahoma Medical Research Foundation, United States
  2. University of Virginia School of Medicine, United States
  3. Howard Hughes Medical Institute, University of Texas Southwestern Medical center, United States
  4. University of Texas Southwestern Medical center, United States
https://doi.org/10.7554/eLife.12902
Share this article
Cite this article
  1. Sushama Sivakumar
  2. Paweł Ł Janczyk
  3. Qianhui Qu
  4. Chad A Brautigam
  5. P Todd Stukenberg
  6. Hongtao Yu
  7. Gary J Gorbsky
(2016)
The human Ska complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores
eLife 5:e12902.
https://doi.org/10.7554/eLife.12902
  2. Download BibTeX
  3. Download .RIS

Abstract

The spindle- and kinetochore-associated (Ska) complex is essential for normal anaphase onset in mitosis. The C-terminal domain (CTD) of Ska1 binds microtubules and was proposed to facilitate kinetochore movement on depolymerizing spindle microtubules. Here we show that Ska complex recruits protein phosphatase 1 (PP1) to kinetochores. This recruitment requires the Ska1 CTD, which binds PP1 in vitro and in human HeLa cells. Ska1 lacking its CTD fused to a PP1-binding peptide or fused directly to PP1 rescues mitotic defects caused by Ska1 depletion. Ska1 fusion to catalytically dead PP1 mutant does not rescue and shows dominant negative effects. Thus, the Ska complex, specifically the Ska1 CTD, recruits PP1 to kinetochores to oppose spindle checkpoint signaling kinases and promote anaphase onset. Microtubule binding by Ska, rather than acting in force production for chromosome movement, may instead serve to promote PP1 recruitment to kinetochores fully attached to spindle microtubules at metaphase.

Article and author information

Author details

  1. Sushama Sivakumar

    Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Paweł Ł Janczyk

    Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Qianhui Qu

    Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Chad A Brautigam

    Department of Biophysics, University of Texas Southwestern Medical center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. P Todd Stukenberg

    Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Hongtao Yu

    Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Gary J Gorbsky

    Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, United States
    For correspondence
    GJG@omrf.org
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Sue Biggins, Fred Hutchinson Cancer Research Center, United States

Version history

  1. Received: November 7, 2015
  2. Accepted: March 3, 2016
  3. Accepted Manuscript published: March 16, 2016 (version 1)
  4. Accepted Manuscript updated: March 21, 2016 (version 2)
  5. Version of Record published: March 29, 2016 (version 3)

Copyright

© 2016, Sivakumar et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,995
    views
  • 751
    downloads
  • 56
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Sushama Sivakumar
  2. Paweł Ł Janczyk
  3. Qianhui Qu
  4. Chad A Brautigam
  5. P Todd Stukenberg
  6. Hongtao Yu
  7. Gary J Gorbsky
(2016)
The human Ska complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores
eLife 5:e12902.
https://doi.org/10.7554/eLife.12902

Share this article

https://doi.org/10.7554/eLife.12902

Categories and tags

Research organism

Further reading

    1. Cell Biology
    2. Chromosomes and Gene Expression

    Heat stress impairs centromere structure and segregation of meiotic chromosomes in Arabidopsis

    Lucie Crhak Khaitova, Pavlina Mikulkova ... Karel Riha
    Research Article

    Heat stress is a major threat to global crop production, and understanding its impact on plant fertility is crucial for developing climate-resilient crops. Despite the known negative effects of heat stress on plant reproduction, the underlying molecular mechanisms remain poorly understood. Here, we investigated the impact of elevated temperature on centromere structure and chromosome segregation during meiosis in Arabidopsis thaliana. Consistent with previous studies, heat stress leads to a decline in fertility and micronuclei formation in pollen mother cells. Our results reveal that elevated temperature causes a decrease in the amount of centromeric histone and the kinetochore protein BMF1 at meiotic centromeres with increasing temperature. Furthermore, we show that heat stress increases the duration of meiotic divisions and prolongs the activity of the spindle assembly checkpoint during meiosis I, indicating an impaired efficiency of the kinetochore attachments to spindle microtubules. Our analysis of mutants with reduced levels of centromeric histone suggests that weakened centromeres sensitize plants to elevated temperature, resulting in meiotic defects and reduced fertility even at moderate temperatures. These results indicate that the structure and functionality of meiotic centromeres in Arabidopsis are highly sensitive to heat stress, and suggest that centromeres and kinetochores may represent a critical bottleneck in plant adaptation to increasing temperatures.

    1. Cell Biology

    High-altitude hypoxia exposure inhibits erythrophagocytosis by inducing macrophage ferroptosis in the spleen

    Wan-ping Yang, Mei-qi Li ... Qian-qian Luo
    Research Article

    High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O2 to investigate these mechanisms. Our findings indicate that HH significantly boosts erythropoiesis, leading to erythrocytosis and splenic changes, including initial contraction to splenomegaly over 14 days. A notable decrease in red pulp macrophages (RPMs) in the spleen, essential for RBCs processing, was observed, correlating with increased iron release and signs of ferroptosis. Prolonged exposure to hypoxia further exacerbated these effects, mirrored in human peripheral blood mononuclear cells. Single-cell sequencing showed a marked reduction in macrophage populations, affecting the spleen’s ability to clear RBCs and contributing to splenomegaly. Our findings suggest splenic ferroptosis contributes to decreased RPMs, affecting erythrophagocytosis and potentially fostering continuous RBCs production in HAPC. These insights could guide the development of targeted therapies for HAPC, emphasizing the importance of splenic macrophages in disease pathology.

    1. Cell Biology

    Golgi Apparatus: Making progress

    Jurgen Denecke
    Insight

    Mapping proteins in and associated with the Golgi apparatus reveals how this cellular compartment emerges in budding yeast and progresses over time.