Zygote morphogenesis but not the establishment of cell polarity in Plasmodium berghei is controlled by the small GTPase, RAB11A

Patil, H., Hughes, K. R., Lemgruber Soares, L. , Philip, N., Dickens, N. , Starnes, G. L. and Waters, A. P. (2020) Zygote morphogenesis but not the establishment of cell polarity in Plasmodium berghei is controlled by the small GTPase, RAB11A. PLoS Pathogens, 16(5), e1008091. (doi: 10.1371/journal.ppat.1008091) (PMID:32463831) (PMCID:PMC7255598)

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Plasmodium species are apicomplexan parasites whose zoites are polarized cells with a marked apical organisation where the organelles associated with host cell invasion and colonization reside. Plasmodium gametes mate in the mosquito midgut to form the spherical and presumed apolar zygote that morphs during the following 24 hours into a polarized, elongated and motile zoite form, the ookinete. Endocytosis-mediated protein transport is generally necessary for the establishment and maintenance of polarity in epithelial cells and neurons, and the small GTPase RAB11A is an important regulator of protein transport via recycling endosomes. PbRAB11A is essential in blood stage asexual of Plasmodium. Therefore, a promoter swap strategy was employed to down-regulate PbRAB11A expression in gametocytes and zygotes of the rodent malaria parasite, Plasmodium berghei which demonstrated the essential role of RAB11A in ookinete development. The approach revealed that lack of PbRAB11A had no effect on gamete production and fertility rates however, the zygote to ookinete transition was almost totally inhibited and transmission through the mosquito was prevented. Lack of PbRAB11A did not prevent meiosis and mitosis, nor the establishment of polarity as indicated by the correct formation and positioning of the Inner Membrane Complex (IMC) and apical complex. However, morphological maturation was prevented and parasites remained spherical and immotile and furthermore, they were impaired in the secretion and distribution of microneme cargo. The data are consistent with the previously proposed model of RAB11A endosome mediated delivery of plasma membrane in Toxoplasma gondii if not its role in IMC formation and implicate it in microneme function.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Dickens, Dr Nicholas and Philip, Dr Nisha and Hughes, Dr Katie and Waters, Professor Andy and Lemgruber Soares, Dr Leandro
Creator Roles:
Hughes, K. R.Conceptualization, Investigation, Methodology, Supervision, Validation, Writing – review and editing
Lemgruber Soares, L.Investigation
Philip, N.Investigation, Methodology
Dickens, N.Formal analysis, Writing – review and editing
Waters, A. P.Conceptualization, Project administration, Supervision, Writing – original draft, Writing – review and editing
Authors: Patil, H., Hughes, K. R., Lemgruber Soares, L., Philip, N., Dickens, N., Starnes, G. L., and Waters, A. P.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:PLoS Pathogens
Publisher:Public Library of Science
ISSN (Online):1553-7374
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in PLoS Pathogens 16(5):e1008091
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
170547The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/ZRIII - Parasitology