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    Recruitment of EB1, a Master Regulator of Microtubule Dynamics, to the Surface of the Theileria annulata Schizont

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    Type
    Article
    Authors
    Woods, Kerry L.
    Theiler, Romina
    Mühlemann, Marcus
    Segiser, Adrian
    Huber, Sandra
    Ansari, Hifzur Rahman cc
    Pain, Arnab cc
    Dobbelaere, Dirk A. E.
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Program
    Computational Bioscience Research Center (CBRC)
    Pathogen Genomics Laboratory
    Date
    2013-05-09
    Permanent link to this record
    http://hdl.handle.net/10754/325345
    
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    Abstract
    The apicomplexan parasite Theileria annulata transforms infected host cells, inducing uncontrolled proliferation and clonal expansion of the parasitized cell population. Shortly after sporozoite entry into the target cell, the surrounding host cell membrane is dissolved and an array of host cell microtubules (MTs) surrounds the parasite, which develops into the transforming schizont. The latter does not egress to invade and transform other cells. Instead, it remains tethered to host cell MTs and, during mitosis and cytokinesis, engages the cell's astral and central spindle MTs to secure its distribution between the two daughter cells. The molecular mechanism by which the schizont recruits and stabilizes host cell MTs is not known. MT minus ends are mostly anchored in the MT organizing center, while the plus ends explore the cellular space, switching constantly between phases of growth and shrinkage (called dynamic instability). Assuming the plus ends of growing MTs provide the first point of contact with the parasite, we focused on the complex protein machinery associated with these structures. We now report how the schizont recruits end-binding protein 1 (EB1), a central component of the MT plus end protein interaction network and key regulator of host cell MT dynamics. Using a range of in vitro experiments, we demonstrate that T. annulata p104, a polymorphic antigen expressed on the schizont surface, functions as a genuine EB1-binding protein and can recruit EB1 in the absence of any other parasite proteins. Binding strictly depends on a consensus SxIP motif located in a highly disordered C-terminal region of p104. We further show that parasite interaction with host cell EB1 is cell cycle regulated. This is the first description of a pathogen-encoded protein to interact with EB1 via a bona-fide SxIP motif. Our findings provide important new insight into the mode of interaction between Theileria and the host cell cytoskeleton. 2013 Woods et al.
    Citation
    Woods KL, Theiler R, Mühlemann M, Segiser A, Huber S, et al. (2013) Recruitment of EB1, a Master Regulator of Microtubule Dynamics, to the Surface of the Theileria annulata Schizont. PLoS Pathog 9: e1003346. doi:10.1371/journal.ppat.1003346.
    Publisher
    Public Library of Science (PLoS)
    Journal
    PLoS Pathogens
    DOI
    10.1371/journal.ppat.1003346
    PubMed ID
    23675298
    PubMed Central ID
    PMC3649978
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.ppat.1003346
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program; Computational Bioscience Research Center (CBRC)

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