The MAP kinase pathway coordinates crossover designation with disassembly of synaptonemal complex proteins during meiosis

  1. Saravanapriah Nadarajan
  2. Firaz Mohideen
  3. Yonatan B Tzur
  4. Nuria Ferrandiz
  5. Oliver Crawley
  6. Alex Montoya
  7. Peter Faull
  8. Ambrosius P Snijders
  9. Pedro R Cutillas
  10. Ashwini Jambhekar
  11. Michael D Blower
  12. Enrique Martinez-Perez
  13. J Wade Harper
  14. Monica P Colaiacovo  Is a corresponding author
  1. Harvard Medical School, United States
  2. Hebrew University of Jerusalem, Israel
  3. Imperial College London, United Kingdom
  4. London Research Institute, United Kingdom
  5. Barts Cancer Institute, United Kingdom

Abstract

Asymmetric disassembly of the synaptonemal complex (SC) is crucial for proper meiotic chromosome segregation. However, the signaling mechanisms that directly regulate this process are poorly understood. Here we show that the mammalian Rho GEF homolog, ECT-2, functions through the conserved RAS/ERK MAP kinase signaling pathway in the C. elegans germline to regulate the disassembly of SC proteins. We find that SYP-2, a SC central region component, is a potential target for MPK-1-mediated phosphorylation and that constitutively phosphorylated SYP-2 impairs the disassembly of SC proteins from chromosomal domains referred to as the long arms of the bivalents. Inactivation of MAP kinase at late pachytene is critical for timely disassembly of the SC proteins from the long arms, and is dependent on the crossover (CO) promoting factors ZHP-3/RNF212/Zip3 and COSA-1/CNTD1. We propose that the conserved MAP kinase pathway coordinates CO designation with the disassembly of SC proteins to ensure accurate chromosome segregation.

Article and author information

Author details

  1. Saravanapriah Nadarajan

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Firaz Mohideen

    Department of Cell Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yonatan B Tzur

    Department of Genetics, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Nuria Ferrandiz

    MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Oliver Crawley

    MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Alex Montoya

    Proteomics facility, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Peter Faull

    Proteomics facility, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Ambrosius P Snijders

    London Research Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Pedro R Cutillas

    Barts Cancer Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Ashwini Jambhekar

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Michael D Blower

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Enrique Martinez-Perez

    MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. J Wade Harper

    Department of Cell Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Monica P Colaiacovo

    Department of Genetics, Harvard Medical School, Boston, United States
    For correspondence
    mcolaiacovo@genetics.med.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Bernard de Massy, Institute of Human Genetics, CNRS UPR 1142, France

Publication history

  1. Received: October 2, 2015
  2. Accepted: February 26, 2016
  3. Accepted Manuscript published: February 27, 2016 (version 1)
  4. Version of Record published: March 14, 2016 (version 2)

Copyright

© 2016, Nadarajan 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.

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  1. Saravanapriah Nadarajan
  2. Firaz Mohideen
  3. Yonatan B Tzur
  4. Nuria Ferrandiz
  5. Oliver Crawley
  6. Alex Montoya
  7. Peter Faull
  8. Ambrosius P Snijders
  9. Pedro R Cutillas
  10. Ashwini Jambhekar
  11. Michael D Blower
  12. Enrique Martinez-Perez
  13. J Wade Harper
  14. Monica P Colaiacovo
(2016)
The MAP kinase pathway coordinates crossover designation with disassembly of synaptonemal complex proteins during meiosis
eLife 5:e12039.
https://doi.org/10.7554/eLife.12039

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