ApiAP2 factors as candidate regulators of stochastic commitment to merozoite production in Theileria annulata

Pieszko, M., Weir, W. , Goodhead, I., Kinnaird, J. and Shiels, B. (2015) ApiAP2 factors as candidate regulators of stochastic commitment to merozoite production in Theileria annulata. PLoS Neglected Tropical Diseases, 9(8), e0003933. (doi: 10.1371/journal.pntd.0003933) (PMID:26273826) (PMCID:PMC4537280)

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Background: Differentiation of one life-cycle stage to the next is critical for survival and transmission of apicomplexan parasites. A number of studies have shown that stage differentiation is a stochastic process and is associated with a point that commits the cell to a change over in the pattern of gene expression. Studies on differentiation to merozoite production (merogony) in T. annulata postulated that commitment involves a concentration threshold of DNA binding proteins and an auto-regulatory loop. Principal Findings: In this study ApiAP2 DNA binding proteins that show changes in expression level during merogony of T. annulata have been identified. DNA motifs bound by orthologous domains in Plasmodium were found to be enriched in upstream regions of stage-regulated T. annulata genes and validated as targets for the T. annulata AP2 domains by electrophoretic mobility shift assay (EMSA). Two findings were of particular note: the gene in T. annulata encoding the orthologue of the ApiAP2 domain in the AP2-G factor that commits Plasmodium to gametocyte production, has an expression profile indicating involvement in transmission of T. annulata to the tick vector; genes encoding related domains that bind, or are predicted to bind, sequence motifs of the type 5'-(A)CACAC(A) are implicated in differential regulation of gene expression, with one gene (TA11145) likely to be preferentially up-regulated via auto-regulation as the cell progresses to merogony. Conclusions: We postulate that the Theileria factor possessing the AP2 domain orthologous to that of Plasmodium AP2-G may regulate gametocytogenesis in a similar manner to AP2-G. In addition, paralogous ApiAP2 factors that recognise 5'-(A)CACAC(A) type motifs could operate in a competitive manner to promote reversible progression towards the point that commits the cell to undergo merogony. Factors possessing AP2 domains that bind (or are predicted to bind) this motif are present in the vector-borne genera Theileria, Babesia and Plasmodium, and other Apicomplexa; leading to the proposal that the mechanisms that control stage differentiation will show a degree of conservation.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Weir, Professor Willie and Shiels, Professor Brian and Goodhead, Dr Ian and Pieszko, Ms Marta and Kinnaird, Dr Jane
Authors: Pieszko, M., Weir, W., Goodhead, I., Kinnaird, J., and Shiels, B.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2015 Pieszko et al.
First Published:First published in PLOS Neglected Tropical Diseases 9(8):e0003933
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
392992An integrated approach for the development of sustainable methods to control tropical theileriosisAndrew TaitWellcome Trust (WELLCOME)075820/A/04/ZSCHOOL OF VETERINARY MEDICINE
531961POSTICK - Post-graduate training network for capacity building to control ticks and tick-borne diseasesBrian ShielsEuropean Commission (EC)238511 POSTICKIII - PARASITOLOGY