Multiple short windows of calcium-dependent protein kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis
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....
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eLife Sciences Publications Ltd
2017-05-01
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Series: | eLife |
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Online Access: | https://elifesciences.org/articles/26524 |
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author | Hanwei Fang Natacha Klages Bastien Baechler Evelyn Hillner Lu Yu Mercedes Pardo Jyoti Choudhary Mathieu Brochet |
author_facet | Hanwei Fang Natacha Klages Bastien Baechler Evelyn Hillner Lu Yu Mercedes Pardo Jyoti Choudhary Mathieu Brochet |
author_sort | Hanwei Fang |
collection | DOAJ |
description | 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. |
first_indexed | 2024-04-12T02:01:20Z |
format | Article |
id | doaj.art-767a468ed788476abc88217a878c09ce |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-12T02:01:20Z |
publishDate | 2017-05-01 |
publisher | eLife Sciences Publications Ltd |
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spelling | doaj.art-767a468ed788476abc88217a878c09ce2022-12-22T03:52:39ZengeLife Sciences Publications LtdeLife2050-084X2017-05-01610.7554/eLife.26524Multiple short windows of calcium-dependent protein kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesisHanwei Fang0Natacha Klages1Bastien Baechler2Evelyn Hillner3Lu Yu4https://orcid.org/0000-0001-8378-9112Mercedes Pardo5https://orcid.org/0000-0002-3477-9695Jyoti Choudhary6Mathieu Brochet7https://orcid.org/0000-0003-3911-5537Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, SwitzerlandDepartment of Microbiology and Molecular Medicine, University of Geneva, Geneva, SwitzerlandDepartment of Microbiology and Molecular Medicine, University of Geneva, Geneva, SwitzerlandProteomic Mass-spectrometry Team, Wellcome Trust Sanger Institute, Cambridge, United KingdomProteomic Mass-spectrometry Team, Wellcome Trust Sanger Institute, Cambridge, United KingdomProteomic Mass-spectrometry Team, Wellcome Trust Sanger Institute, Cambridge, United KingdomProteomic Mass-spectrometry Team, Wellcome Trust Sanger Institute, Cambridge, United KingdomDepartment of Microbiology and Molecular Medicine, University of Geneva, Geneva, SwitzerlandMalaria 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.https://elifesciences.org/articles/26524signallingcalciumcell cyclemalariaprotein kinasePlasmodium berghei |
spellingShingle | Hanwei Fang Natacha Klages Bastien Baechler Evelyn Hillner Lu Yu Mercedes Pardo Jyoti Choudhary Mathieu Brochet Multiple short windows of calcium-dependent protein kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis eLife signalling calcium cell cycle malaria protein kinase Plasmodium berghei |
title | Multiple short windows of calcium-dependent protein kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis |
title_full | Multiple short windows of calcium-dependent protein kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis |
title_fullStr | Multiple short windows of calcium-dependent protein kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis |
title_full_unstemmed | Multiple short windows of calcium-dependent protein kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis |
title_short | Multiple short windows of calcium-dependent protein kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis |
title_sort | multiple short windows of calcium dependent protein kinase 4 activity coordinate distinct cell cycle events during plasmodium gametogenesis |
topic | signalling calcium cell cycle malaria protein kinase Plasmodium berghei |
url | https://elifesciences.org/articles/26524 |
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