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dc.contributor.authorWoods, Kerry L.
dc.contributor.authorTheiler, Romina
dc.contributor.authorMühlemann, Marcus
dc.contributor.authorSegiser, Adrian
dc.contributor.authorHuber, Sandra
dc.contributor.authorAnsari, Hifzur Rahman
dc.contributor.authorPain, Arnab
dc.contributor.authorDobbelaere, Dirk A. E.
dc.date.accessioned2014-08-27T09:48:26Z
dc.date.available2014-08-27T09:48:26Z
dc.date.issued2013-05-09
dc.identifier.citationWoods 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.
dc.identifier.issn15537366
dc.identifier.pmid23675298
dc.identifier.doi10.1371/journal.ppat.1003346
dc.identifier.urihttp://hdl.handle.net/10754/325345
dc.description.abstractThe 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.
dc.language.isoen
dc.publisherPublic Library of Science (PLoS)
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rightsArchived with thanks to PLoS Pathogens
dc.subjectcell surface protein
dc.subjectcomplementary DNA
dc.subjectend binding protein 1
dc.subjectunclassified drug
dc.subjectanimal cell
dc.subjectcell cycle
dc.subjectcell growth
dc.subjectcell screening
dc.subjectcell tracking
dc.subjectcontrolled study
dc.subjectcytoskeleton
dc.subjecthost cell
dc.subjecthost parasite interaction
dc.subjectimmunoblotting
dc.subjectimmunofluorescence
dc.subjectimmunofluorescence microscopy
dc.subjectmicroinjection
dc.subjectmicrotubule
dc.subjectmolecular docking
dc.subjectnucleotide sequence
dc.subjectpolyacrylamide gel electrophoresis
dc.subjectpolymerase chain reaction
dc.subjectprotein expression
dc.subjectprotein interaction
dc.subjectprotein phosphorylation
dc.subjectschizont
dc.subjectsequence analysis
dc.subjectTheileria annulata
dc.subjecttime lapse imaging
dc.subjectWestern blotting
dc.subjectAmino Acid Sequence
dc.subjectAntigens, Protozoan
dc.subjectBlotting, Western
dc.subjectCattle
dc.subjectCercopithecus aethiops
dc.subjectCOS Cells
dc.subjectFluorescent Antibody Technique
dc.subjectHost-Parasite Interactions
dc.subjectMice
dc.subjectMicrotubule-Associated Proteins
dc.subjectMicrotubules
dc.subjectMolecular Sequence Data
dc.subjectProtein Transport
dc.subjectSchizonts
dc.subjectTheileria annulata
dc.subjectTheileria
dc.subjectTheileria annulata
dc.titleRecruitment of EB1, a Master Regulator of Microtubule Dynamics, to the Surface of the Theileria annulata Schizont
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.contributor.departmentComputational Bioscience Research Center (CBRC)
dc.contributor.departmentPathogen Genomics Laboratory
dc.identifier.journalPLoS Pathogens
dc.identifier.pmcidPMC3649978
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionMolecular Pathobiology, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland
dc.contributor.institutionResearch Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka, Japan
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)
kaust.personAnsari, Hifzur Rahman
kaust.personPain, Arnab
refterms.dateFOA2018-06-13T15:16:06Z


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