Atypical Mitogen-activated Protein Kinase Phosphatase Implicated in Regulating Transition from Pre-S-Phase Asexual Intraerythrocytic Development of Plasmodium falciparum

Date
2013
Authors
Balu, Bharath
Campbell, Christopher
Sedillo, Jennifer
Maher, Steven
Singh, Naresh
Thomas, Phaedra
Zhang, Min
Pance, Alena
Otto, Thomas D.
Rayner, Julian C.
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Publisher
Eukaryotic Cell
Abstract
Intraerythrocytic development of the human malaria parasite Plasmodium falciparum appears as a continuous flow through growth and proliferation. To develop a greater understanding of the critical regulatory events, we utilized piggyBac insertional mutagenesis to randomly disrupt genes. Screening a collection of piggyBac mutants for slow growth, we isolated the attenuated parasite C9, which carried a single insertion disrupting the open reading frame (ORF) of PF3D7_1305500. This gene encodes a protein structurally similar to a mitogen-activated protein kinase (MAPK) phosphatase, except for two notable characteristics that alter the signature motif of the dual-specificity phosphatase domain, suggesting that it may be a low-activity phosphatase or pseudophosphatase. C9 parasites demonstrated a significantly lower growth rate with delayed entry into the S/M phase of the cell cycle, which follows the stage of maximum PF3D7_1305500 expression in intact parasites. Genetic complementation with the full-length PF3D7_1305500 rescued the wild-type phenotype of C9, validating the importance of the putative protein phosphatase PF3D7_1305500 as a regulator of pre-S-phase cell cycle progression in P. falciparum.
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Citation
Balu, B., Campbell, C., Sedillo, J., Maher, S., Singh, N., Thomas, P., Zhang, M., Pance, A., Otto, T. D., Rayner, J. C., & Adams, J. H. (2013). Atypical mitogen-activated protein kinase phosphatase implicated in regulating transition from pre-S-Phase asexual intraerythrocytic development of Plasmodium falciparum. Eukaryotic Cell, 12(9), 1171–1178. https://doi.org/10.1128/EC.00028-13