Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation

Summary: The transmission of malaria parasites to mosquitoes relies on the rapid induction of sexual reproduction upon their ingestion into a blood meal. Haploid female and male gametocytes become activated and emerge from their host cells, and the males enter the cell cycle to produce eight microga...

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Main Authors: Brandon M. Invergo, Mathieu Brochet, Lu Yu, Jyoti Choudhary, Pedro Beltrao, Oliver Billker
Format: Article
Language:English
Published: Elsevier 2017-11-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124717315346
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author Brandon M. Invergo
Mathieu Brochet
Lu Yu
Jyoti Choudhary
Pedro Beltrao
Oliver Billker
author_facet Brandon M. Invergo
Mathieu Brochet
Lu Yu
Jyoti Choudhary
Pedro Beltrao
Oliver Billker
author_sort Brandon M. Invergo
collection DOAJ
description Summary: The transmission of malaria parasites to mosquitoes relies on the rapid induction of sexual reproduction upon their ingestion into a blood meal. Haploid female and male gametocytes become activated and emerge from their host cells, and the males enter the cell cycle to produce eight microgametes. The synchronized nature of gametogenesis allowed us to investigate phosphorylation signaling during its first minute in Plasmodium berghei via a high-resolution time course of the phosphoproteome. This revealed an unexpectedly broad response, with proteins related to distinct cell cycle events undergoing simultaneous phosphoregulation. We implicate several protein kinases in the process, and we validate our analyses on the plant-like calcium-dependent protein kinase 4 (CDPK4) and a homolog of serine/arginine-rich protein kinases (SRPK1). Mutants in these kinases displayed distinct phosphoproteomic disruptions, consistent with differences in their phenotypes. The results reveal the central role of protein phosphorylation in the atypical cell cycle regulation of a divergent eukaryote. : Invergo et al. measure a phosphoproteomic time course during a life cycle transition of a malarial parasite. They observed broad phosphoregulation on a sub-minute scale, including simultaneous regulation of replication- and mitosis-related proteins. Their analyses reveal conserved phosphorylation patterns, and they highlight functional roles of specific protein kinases during this process. Keywords: gametogenesis, proteomics, signal transduction, ARK2, CRK5
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spelling doaj.art-3b3a7966127b4c5f80213dce7b6035e82022-12-21T18:53:55ZengElsevierCell Reports2211-12472017-11-0121720172029Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete FormationBrandon M. Invergo0Mathieu Brochet1Lu Yu2Jyoti Choudhary3Pedro Beltrao4Oliver Billker5European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire CB10 1SD, UK; Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UKMalaria Programme, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK; Department of Microbiology & Molecular Medicine, CMU, University of Geneva, 1211 Geneva 4, Geneva, SwitzerlandProteomics Mass Spectrometry, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK; The Institute of Cancer Research, Chester Betty Laboratory, London, Greater London SW7 3RP, UKProteomics Mass Spectrometry, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK; The Institute of Cancer Research, Chester Betty Laboratory, London, Greater London SW7 3RP, UK; Corresponding authorEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire CB10 1SD, UK; Corresponding authorMalaria Programme, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK; Corresponding authorSummary: The transmission of malaria parasites to mosquitoes relies on the rapid induction of sexual reproduction upon their ingestion into a blood meal. Haploid female and male gametocytes become activated and emerge from their host cells, and the males enter the cell cycle to produce eight microgametes. The synchronized nature of gametogenesis allowed us to investigate phosphorylation signaling during its first minute in Plasmodium berghei via a high-resolution time course of the phosphoproteome. This revealed an unexpectedly broad response, with proteins related to distinct cell cycle events undergoing simultaneous phosphoregulation. We implicate several protein kinases in the process, and we validate our analyses on the plant-like calcium-dependent protein kinase 4 (CDPK4) and a homolog of serine/arginine-rich protein kinases (SRPK1). Mutants in these kinases displayed distinct phosphoproteomic disruptions, consistent with differences in their phenotypes. The results reveal the central role of protein phosphorylation in the atypical cell cycle regulation of a divergent eukaryote. : Invergo et al. measure a phosphoproteomic time course during a life cycle transition of a malarial parasite. They observed broad phosphoregulation on a sub-minute scale, including simultaneous regulation of replication- and mitosis-related proteins. Their analyses reveal conserved phosphorylation patterns, and they highlight functional roles of specific protein kinases during this process. Keywords: gametogenesis, proteomics, signal transduction, ARK2, CRK5http://www.sciencedirect.com/science/article/pii/S2211124717315346
spellingShingle Brandon M. Invergo
Mathieu Brochet
Lu Yu
Jyoti Choudhary
Pedro Beltrao
Oliver Billker
Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation
Cell Reports
title Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation
title_full Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation
title_fullStr Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation
title_full_unstemmed Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation
title_short Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation
title_sort sub minute phosphoregulation of cell cycle systems during plasmodium gamete formation
url http://www.sciencedirect.com/science/article/pii/S2211124717315346
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