Literature DB >> 17512410

Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse.

Tasha N Sims1, Timothy J Soos, Harry S Xenias, Benjamin Dubin-Thaler, Jake M Hofman, Janelle C Waite, Thomas O Cameron, V Kaye Thomas, Rajat Varma, Chris H Wiggins, Michael P Sheetz, Dan R Littman, Michael L Dustin.   

Abstract

The immunological synapse (IS) is a junction between the T cell and antigen-presenting cell and is composed of supramolecular activation clusters (SMACs). No studies have been published on naive T cell IS dynamics. Here, we find that IS formation during antigen recognition comprises cycles of stable IS formation and autonomous naive T cell migration. The migration phase is driven by PKCtheta, which is localized to the F-actin-dependent peripheral (p)SMAC. PKCtheta(-/-) T cells formed hyperstable IS in vitro and in vivo and, like WT cells, displayed fast oscillations in the distal SMAC, but they showed reduced slow oscillations in pSMAC integrity. IS reformation is driven by the Wiscott Aldrich Syndrome protein (WASp). WASp(-/-) T cells displayed normal IS formation but were unable to reform IS after migration unless PKCtheta was inhibited. Thus, opposing effects of PKCtheta and WASp control IS stability through pSMAC symmetry breaking and reformation.

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Year:  2007        PMID: 17512410     DOI: 10.1016/j.cell.2007.03.037

Source DB:  PubMed          Journal:  Cell        ISSN: 0092-8674            Impact factor:   41.582


  185 in total

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