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Sci Rep. 2018 Apr 4;8(1):5610. doi: 10.1038/s41598-018-23871-9.

Plasmodium APC3 mediates chromosome condensation and cytokinesis during atypical mitosis in male gametogenesis.

Author information

1
School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
2
The Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, UK.
3
Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford, UK.
4
Leiden Malaria Research Group, Parasitology, Center of Infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
5
Protein and Nucleic Acid Chemistry Laboratory, Centre for Core Biotechnology Services, University of Leicester, Leicester, UK.
6
Department of Molecular and Cell Biology, University of Leicester, Leicester, UK.
7
UCL Cancer Institute, University College London, London, UK.
8
The Francis Crick Institute, London, UK.
9
The Leicester Cancer Research Centre, College of Life Sciences, University of Leicester, Leicester, UK.
10
School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK. rita.tewari@nottingham.ac.uk.

Abstract

The anaphase promoting complex/cyclosome (APC/C) is a highly conserved multi-subunit E3 ubiquitin ligase that controls mitotic division in eukaryotic cells by tagging cell cycle regulators for proteolysis. APC3 is a key component that contributes to APC/C function. Plasmodium, the causative agent of malaria, undergoes atypical mitotic division during its life cycle. Only a small subset of APC/C components has been identified in Plasmodium and their involvement in atypical cell division is not well understood. Here, using reverse genetics we examined the localisation and function of APC3 in Plasmodium berghei. APC3 was observed as a single focus that co-localised with the centriolar plaque during asexual cell division in schizonts, whereas it appeared as multiple foci in male gametocytes. Functional studies using gene disruption and conditional knockdown revealed essential roles of APC3 during these mitotic stages with loss resulting in a lack of chromosome condensation, abnormal cytokinesis and absence of microgamete formation. Overall, our data suggest that Plasmodium utilises unique cell cycle machinery to coordinate various processes during endomitosis, and this warrants further investigation in future studies.

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