An Experimental and Computational Study of Effects of Microtubule Stabilization on T-Cell Polarity 英文参考文献.docVIP
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An Experimental and Computational Study of Effects of Microtubule Stabilization on T-Cell Polarity 英文参考文献
AnExperimentalandComputationalStudyofEffectsof
MicrotubuleStabilizationonT-CellPolarity
ArieBaratt.,SergeyN.Arkhipov.,IvanV.Maly*
DepartmentofComputationalBiology,UniversityofPittsburghSchoolofMedicine,Pittsburgh,Pennsylvania,UnitedStatesofAmerica
Abstract
T-killer cells eliminate infected and cancerous cells with precision by positioning their centrosome near the interface
(immunological synapse) with the target cell. The mechanism of centrosome positioning has remained controversial, in
particular the role of microtubule dynamics in it. We re-examined the issue in the experimental model of Jurkat cells
presented with a T cell receptor-binding artificial substrate, which permits controlled stimulation and reproducible
measurements.Neither1-mMtaxolnor100-nMnocodazoleinhibitedthecentrosomepositioningatthe``synapsewiththe
biomimeticsubstrate.Atthesametime,inmicromolartaxolbutnotinnanomolarnocodazolethecentrosomeadopteda
distinct peripheral rather than the normally central position within the synapse. This effect was reproduced in a
computationalenergy-minimizationmodelthatassumednomicrotubuledynamics,butonlyataxol-inducedincreaseinthe
lengthofthemicrotubules.Together,theexperimentalandcomputationalresultsindicatethatmicrotubuledynamicsare
not essential for the centrosome positioning, but that the fit of the microtubule array in the deformed body of the
conjugatedTcellisamajorfactor.ThepossibilityofmodulatingtheT-cellcentrosomepositionwithwell-studieddrugsand
ofpredictingtheireffectsinsilicoappearsattractivefordesigninganti-cancerandantiviraltherapies.
Citation:BarattA,ArkhipovSN,MalyIV(2008)AnExperimentalandComputationalStudyofEffectsofMicrotubuleStabilizationonT-CellPolarity.PLoSONE3
(12):e3861.doi:10.1371/journal.pone.0003861
Editor:DeryaUnutmaz,NewYorkUniversitySchoolofMedicine,UnitedStatesofAmerica
ReceivedJuly29,2008;AcceptedNovember12,2008;PublishedDecember8,2008
Copyright: ? 2008 Baratt et al. This is an open-access article distributed under the terms of the
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