Multiple short windows of Calcium-Dependent Protein Kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis
- University of Geneva, Switzerland
- Wellcome Trust Sanger Institute, United Kingdom
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.
Data availability
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CDPK4 is a pleiotropic regulator controlling the atypical Plasmodium cell cycle during mosquito transmissionPublicly available at the EMBl-EBI Pride Archive (accession no: PXD005884).
Article and author information
Author details
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.
Reviewing Editor
- Elena Levashina, Max Planck Institute for Infection Biology, Germany
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.
Version history
- Received: March 3, 2017
- Accepted: April 27, 2017
- Accepted Manuscript published: May 8, 2017 (version 1)
- 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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Multiple short windows of Calcium-Dependent Protein Kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis
eLife 6:e26524.
https://doi.org/10.7554/eLife.26524
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