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

Handle URI:
http://hdl.handle.net/10754/325345
Title:
Recruitment of EB1, a Master Regulator of Microtubule Dynamics, to the Surface of the Theileria annulata Schizont
Authors:
Woods, Kerry L.; Theiler, Romina; Mühlemann, Marcus; Segiser, Adrian; Huber, Sandra; Ansari, Hifzur R.; Pain, Arnab ( 0000-0002-1755-2819 ) ; Dobbelaere, Dirk A. E.
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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Computational Bioscience Research Center (CBRC)
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
Issue Date:
9-May-2013
DOI:
10.1371/journal.ppat.1003346
PubMed ID:
23675298
PubMed Central ID:
PMC3649978
Type:
Article
ISSN:
15537366
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorWoods, Kerry L.en
dc.contributor.authorTheiler, Rominaen
dc.contributor.authorMühlemann, Marcusen
dc.contributor.authorSegiser, Adrianen
dc.contributor.authorHuber, Sandraen
dc.contributor.authorAnsari, Hifzur R.en
dc.contributor.authorPain, Arnaben
dc.contributor.authorDobbelaere, Dirk A. E.en
dc.date.accessioned2014-08-27T09:48:26Zen
dc.date.available2014-08-27T09:48:26Zen
dc.date.issued2013-05-09en
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.en
dc.identifier.issn15537366en
dc.identifier.pmid23675298en
dc.identifier.doi10.1371/journal.ppat.1003346en
dc.identifier.urihttp://hdl.handle.net/10754/325345en
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.en
dc.language.isoenen
dc.publisherPublic Library of Science (PLoS)en
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.en
dc.rightsArchived with thanks to PLoS Pathogensen
dc.subjectcell surface proteinen
dc.subjectcomplementary DNAen
dc.subjectend binding protein 1en
dc.subjectunclassified drugen
dc.subjectanimal cellen
dc.subjectcell cycleen
dc.subjectcell growthen
dc.subjectcell screeningen
dc.subjectcell trackingen
dc.subjectcontrolled studyen
dc.subjectcytoskeletonen
dc.subjecthost cellen
dc.subjecthost parasite interactionen
dc.subjectimmunoblottingen
dc.subjectimmunofluorescenceen
dc.subjectimmunofluorescence microscopyen
dc.subjectmicroinjectionen
dc.subjectmicrotubuleen
dc.subjectmolecular dockingen
dc.subjectnucleotide sequenceen
dc.subjectpolyacrylamide gel electrophoresisen
dc.subjectpolymerase chain reactionen
dc.subjectprotein expressionen
dc.subjectprotein interactionen
dc.subjectprotein phosphorylationen
dc.subjectschizonten
dc.subjectsequence analysisen
dc.subjectTheileria annulataen
dc.subjecttime lapse imagingen
dc.subjectWestern blottingen
dc.subjectAmino Acid Sequenceen
dc.subjectAntigens, Protozoanen
dc.subjectBlotting, Westernen
dc.subjectCattleen
dc.subjectCercopithecus aethiopsen
dc.subjectCOS Cellsen
dc.subjectFluorescent Antibody Techniqueen
dc.subjectHost-Parasite Interactionsen
dc.subjectMiceen
dc.subjectMicrotubule-Associated Proteinsen
dc.subjectMicrotubulesen
dc.subjectMolecular Sequence Dataen
dc.subjectProtein Transporten
dc.subjectSchizontsen
dc.subjectTheileria annulataen
dc.subjectTheileriaen
dc.subjectTheileria annulataen
dc.titleRecruitment of EB1, a Master Regulator of Microtubule Dynamics, to the Surface of the Theileria annulata Schizonten
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalPLoS Pathogensen
dc.identifier.pmcidPMC3649978en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionMolecular Pathobiology, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerlanden
dc.contributor.institutionResearch Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka, Japanen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorAnsari, Hifzur Rahmanen
kaust.authorPain, Arnaben

Related articles on PubMed

All Items in KAUST are protected by copyright, with all rights reserved, unless otherwise indicated.