Unique apicomplexan IMC sub-compartment proteins are early markers for apical polarity in the malaria parasite
Benoit Poulin,
Eva-Maria Patzewitz,
Declan Brady,
Olivier Silvie,
Megan H. Wright,
David J. P. Ferguson,
Richard J. Wall,
Sarah Whipple,
David S. Guttery,
Edward W. Tate,
Bill Wickstead,
Anthony A. Holder,
Rita Tewari
Affiliations
Benoit Poulin
Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK
Eva-Maria Patzewitz
Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK
Declan Brady
Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK
Olivier Silvie
INSERM and Université Pierre et Marie Curie, UMR_S 945 “Immunity and infection”, Centre Hospitalier Universitaire Pitié-Salpêtrière, 75013 Paris, France
Megan H. Wright
Institute of Chemical Biology, Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK
David J. P. Ferguson
Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK
Richard J. Wall
Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK
Sarah Whipple
Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK
David S. Guttery
Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK
Edward W. Tate
Institute of Chemical Biology, Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK
Bill Wickstead
Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK
Anthony A. Holder
Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
Rita Tewari
Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK
Summary The phylum Apicomplexa comprises over 5000 intracellular protozoan parasites, including Plasmodium and Toxoplasma, that are clinically important pathogens affecting humans and livestock. Malaria parasites belonging to the genus Plasmodium possess a pellicle comprised of a plasmalemma and inner membrane complex (IMC), which is implicated in parasite motility and invasion. Using live cell imaging and reverse genetics in the rodent malaria model P. berghei, we localise two unique IMC sub-compartment proteins (ISPs) and examine their role in defining apical polarity during zygote (ookinete) development. We show that these proteins localise to the anterior apical end of the parasite where IMC organisation is initiated, and are expressed at all developmental stages, especially those that are invasive. Both ISP proteins are N-myristoylated, phosphorylated and membrane-bound. Gene disruption studies suggest that ISP1 is likely essential for parasite development, whereas ISP3 is not. However, an absence of ISP3 alters the apical localisation of ISP1 in all invasive stages including ookinetes and sporozoites, suggesting a coordinated function for these proteins in the organisation of apical polarity in the parasite.
