1. Cell Biology
  2. Microbiology and Infectious Disease
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Multiple short windows of Calcium-Dependent Protein Kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis

  1. Hanwei Fang
  2. Natacha Klages
  3. Bastien Baechler
  4. Evelyn Hillner
  5. Lu Yu
  6. Mercedes Pardo
  7. Jyoti Choudhary
  8. Mathieu Brochet  Is a corresponding author
  1. University of Geneva, Switzerland
  2. Wellcome Trust Sanger Institute, United Kingdom
Research Article
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Cite this article as: eLife 2017;6:e26524 doi: 10.7554/eLife.26524

Abstract

Malaria transmission relies on the production of gametes following ingestion by a mosquito. Here, we show that Ca2+-dependent protein kinase 4 controls three processes essential to progress from a single haploid microgametocyte to the release of eight flagellated microgametes in Plasmodium berghei. A myristoylated isoform is activated by Ca2+ to initiate a first genome replication within twenty seconds of activation. This role is mediated by a protein of the SAPS-domain family involved in S-phase entry. At the same time, CDPK4 is required for the assembly of the subsequent mitotic spindle and to phosphorylate a microtubule-associated protein important for mitotic spindle formation. Finally, a non-myristoylated isoform is essential to complete cytokinesis by activating motility of the male flagellum. This role has been linked to phosphorylation of an uncharacterised flagellar protein. Altogether, this study reveals how a kinase integrates and transduces multiple signals to control key cell-cycle transitions during Plasmodium gametogenesis.

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The following data sets were generated

Article and author information

Author details

  1. Hanwei Fang

    Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Natacha Klages

    Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Bastien Baechler

    Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Evelyn Hillner

    Proteomic Mass-spectrometry Team, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Lu Yu

    Proteomic Mass-spectrometry Team, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8378-9112
  6. Mercedes Pardo

    Proteomic Mass-spectrometry Team, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3477-9695
  7. Jyoti Choudhary

    Proteomic Mass-spectrometry Team, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Mathieu Brochet

    Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland
    For correspondence
    Mathieu.Brochet@unige.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3911-5537

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (BSSGI0_155852)

  • Mathieu Brochet

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments were conducted with the authorization Number (GE/82/15 and GE/41/17) according to the guidelines and regulations issued by the Swiss Federal Veterinary Office.

Reviewing Editor

  1. Elena Levashina, Max Planck Institute for Infection Biology, Germany

Publication history

  1. Received: March 3, 2017
  2. Accepted: April 27, 2017
  3. Accepted Manuscript published: May 8, 2017 (version 1)
  4. Version of Record published: June 2, 2017 (version 2)

Copyright

© 2017, Fang 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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