Plasmodium Condensin Core Subunits SMC2/SMC4 Mediate Atypical Mitosis and Are Essential for Parasite Proliferation and Transmission
Rajan Pandey,
Steven Abel,
Matthew Boucher,
Richard J. Wall,
Mohammad Zeeshan,
Edward Rea,
Aline Freville,
Xueqing Maggie Lu,
Declan Brady,
Emilie Daniel,
Rebecca R. Stanway,
Sally Wheatley,
Gayani Batugedara,
Thomas Hollin,
Andrew R. Bottrill,
Dinesh Gupta,
Anthony A. Holder,
Karine G. Le Roch,
Rita Tewari
Affiliations
Rajan Pandey
School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
Steven Abel
Department of Molecular, Cell and Systems Biology, University of California Riverside, 900 University Ave., Riverside, CA 92521, USA
Matthew Boucher
School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
Richard J. Wall
Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
Mohammad Zeeshan
School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
Edward Rea
School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
Aline Freville
School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
Xueqing Maggie Lu
Department of Molecular, Cell and Systems Biology, University of California Riverside, 900 University Ave., Riverside, CA 92521, USA
Declan Brady
School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
Emilie Daniel
School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
Rebecca R. Stanway
Institute of Cell Biology, University of Bern, Bern 3012, Switzerland
Sally Wheatley
School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
Gayani Batugedara
Department of Molecular, Cell and Systems Biology, University of California Riverside, 900 University Ave., Riverside, CA 92521, USA
Thomas Hollin
Department of Molecular, Cell and Systems Biology, University of California Riverside, 900 University Ave., Riverside, CA 92521, USA
Andrew R. Bottrill
School of Life Sciences, Gibbet Hill Campus, University of Warwick, Coventry CV4 7AL, UK
Dinesh Gupta
Translational Bioinformatics Group, International Center for Genetic Engineering and Biotechnology, New Delhi 110067, India
Anthony A. Holder
Malaria Parasitology Laboratory, The Francis Crick Institute, London NW1 1AT, UK
Karine G. Le Roch
Department of Molecular, Cell and Systems Biology, University of California Riverside, 900 University Ave., Riverside, CA 92521, USA; Corresponding author
Rita Tewari
School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK; Corresponding author
Summary: Condensin is a multi-subunit protein complex regulating chromosome condensation and segregation during cell division. In Plasmodium spp., the causative agent of malaria, cell division is atypical and the role of condensin is unclear. Here we examine the role of SMC2 and SMC4, the core subunits of condensin, during endomitosis in schizogony and endoreduplication in male gametogenesis. During early schizogony, SMC2/SMC4 localize to a distinct focus, identified as the centromeres by NDC80 fluorescence and chromatin immunoprecipitation sequencing (ChIP-seq) analyses, but do not form condensin I or II complexes. In mature schizonts and during male gametogenesis, there is a diffuse SMC2/SMC4 distribution on chromosomes and in the nucleus, and both condensin I and condensin II complexes form at these stages. Knockdown of smc2 and smc4 gene expression reveals essential roles in parasite proliferation and transmission. The condensin core subunits (SMC2/SMC4) form different complexes and may have distinct functions at various stages of the parasite life cycle. : Pandey et al. use live cell imaging, proteomics, and genetic approaches to show that Plasmodium condensin core subunits (SMC2/SMC4) have differential cellular location and condensin complex formation during parasite development and have essential roles in parasite proliferation and transmission. Keywords: condensin, SMC4, atypical mitosis, Plasmodium, mosquito, transmision, chromosome, protein complex, kleisin, oocyst