Inducing controlled cell cycle arrest and re-entry during asexual proliferation of Plasmodium falciparum malaria parasites

Autor:	Hilde von Grüning, Jandeli Niemand, Bianca Brider, Werner Smidt, Riëtte van Biljon, Janette Reader, Clarissa Abrie, Annel Smit, Roelof Dj van Wyk, Lyn-Marie Birkholtz, Heather J. Painter, Manuel Llinás, Christian Doerig, Katherine Clark
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	DNA Replication 0301 basic medicine Eflornithine Cell cycle checkpoint Cell division Plasmodium falciparum 030106 microbiology Cell Protozoan Proteins lcsh:Medicine Biology Plasmodium Article 03 medical and health sciences 0302 clinical medicine Polyamines medicine NIMA-Related Kinases lcsh:Science Transcription factor 030304 developmental biology 0303 health sciences Multidisciplinary Cell Cycle lcsh:R Cell cycle medicine.disease biology.organism_classification 3. Good health Cell biology DNA-Binding Proteins 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis lcsh:Q Malaria Transcription Factors
Zdroj:	Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) Scientific Reports
ISSN:	2045-2322
Popis:	The life cycle of the malaria parasitePlasmodium falciparumis tightly regulated, oscillating between stages of intense proliferation and quiescence. Cyclic 48-hour asexual replication ofPlasmodiumis markedly different from cell division in higher eukaryotes, and mechanistically poorly understood. Here, we report tight synchronisation of malaria parasites during the early phases of the cell cycle by exposure to DL-α-difluoromethylornithine (DFMO), which results in the depletion of polyamines. This induces an inescapable cell cycle arrest in G1(~15 hours post-invasion) by blocking G1/S transition. Cell cycle-arrested parasites enter a quiescent G0-like state but, upon addition of exogenous polyamines, re-initiate their cell cycle in a coordinated fashion. This ability to halt malaria parasites at a specific point in their cell cycle, and to subsequently trigger re-entry into the cell cycle, provides a valuable framework to investigate cell cycle regulation in these parasites. We therefore used gene expression analyses to show that re-entry into the cell cycle involves expression of Ca2+-sensitive (cdpk4andpk2)and mitotic kinases (nimaandark2),with deregulation of the pre-replicative complex associated with expression ofpk2. Changes in gene expression could be driven through transcription factors MYB1 and two ApiAP2 family members. This new approach to parasite synchronisation therefore expands our currently limited toolkit to investigate cell cycle regulation in malaria parasites.
Databáze:	OpenAIRE
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