Distinct mechanisms regulate Lck spatial organization in activated T cells
Phosphorylation of the T cell receptor (TCR) by the kinase Lck is the first detectable signaling event upon antigen engagement. The distribution of Lck within the plasma membrane, its conformational state, kinase activity and protein interactions all contribute to determine how efficiently Lck phosp...
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doaj-3a006b2a1c9d4cf9a64ed540cfa4449f2020-11-25T01:11:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242016-03-01710.3389/fimmu.2016.00083175388Distinct mechanisms regulate Lck spatial organization in activated T cellsNatasha eKapoor-Kaushik0Elizabeth eHinde1Elizabeth eHinde2Ewoud Bernardus Compeer3Yui eYamamoto4Yui eYamamoto5Felix eKraus6Zhengmin eYang7Zhengmin eYang8Jieqiong eLou9Jieqiong eLou10Thibault eTabarin11Thibault eTabarin12Sophie Victoria Pageon13Sophie Victoria Pageon14Katharina eGaus15Katharina eGaus16Jeremie eRossy17Jeremie eRossy18University of New South WalesUniversity of New South WalesARC Centre of Excellence in Advanced Molecular ImagingUniversity of New South WalesUniversity of New South WalesARC Centre of Excellence in Advanced Molecular ImagingUniversity of New South WalesUniversity of New South WalesARC Centre of Excellence in Advanced Molecular ImagingUniversity of New South WalesARC Centre of Excellence in Advanced Molecular ImagingUniversity of New South WalesARC Centre of Excellence in Advanced Molecular ImagingUniversity of New South WalesARC Centre of Excellence in Advanced Molecular ImagingUniversity of New South WalesARC Centre of Excellence in Advanced Molecular ImagingUniversity of New South WalesARC Centre of Excellence in Advanced Molecular ImagingPhosphorylation of the T cell receptor (TCR) by the kinase Lck is the first detectable signaling event upon antigen engagement. The distribution of Lck within the plasma membrane, its conformational state, kinase activity and protein interactions all contribute to determine how efficiently Lck phosphorylates the engaged TCR. Here we used cross-correlation raster image spectroscopy (ccRICS) and photoactivated localization microscopy (PALM) to identify two mechanisms of Lck clustering: an intrinsic mechanism of Lck clustering induced by locking Lck in its open conformation, and an extrinsic mechanism of clustering controlled by the phosphorylation of tyrosine 192, which regulates the affinity of Lck SH2 domain. Both mechanisms of clustering were differently affected by the absence of the kinase Zap70 or the adaptor Lat. We further observed that the adaptor TSAd bound to and promoted the diffusion of Lck when it is phosphorylated on tyrosine 192. Our data suggest that while Lck open conformation drives aggregation and clustering, the spatial organization of Lck is further controlled by signaling events downstream of TCR phosphorylation.http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00083/fullLckT cell signalingMembrane organizationimage correlation spectroscopySuper-resolution fluorescence microscopyassembly of signaling complexes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Natasha eKapoor-Kaushik Elizabeth eHinde Elizabeth eHinde Ewoud Bernardus Compeer Yui eYamamoto Yui eYamamoto Felix eKraus Zhengmin eYang Zhengmin eYang Jieqiong eLou Jieqiong eLou Thibault eTabarin Thibault eTabarin Sophie Victoria Pageon Sophie Victoria Pageon Katharina eGaus Katharina eGaus Jeremie eRossy Jeremie eRossy |
spellingShingle |
Natasha eKapoor-Kaushik Elizabeth eHinde Elizabeth eHinde Ewoud Bernardus Compeer Yui eYamamoto Yui eYamamoto Felix eKraus Zhengmin eYang Zhengmin eYang Jieqiong eLou Jieqiong eLou Thibault eTabarin Thibault eTabarin Sophie Victoria Pageon Sophie Victoria Pageon Katharina eGaus Katharina eGaus Jeremie eRossy Jeremie eRossy Distinct mechanisms regulate Lck spatial organization in activated T cells Frontiers in Immunology Lck T cell signaling Membrane organization image correlation spectroscopy Super-resolution fluorescence microscopy assembly of signaling complexes |
author_facet |
Natasha eKapoor-Kaushik Elizabeth eHinde Elizabeth eHinde Ewoud Bernardus Compeer Yui eYamamoto Yui eYamamoto Felix eKraus Zhengmin eYang Zhengmin eYang Jieqiong eLou Jieqiong eLou Thibault eTabarin Thibault eTabarin Sophie Victoria Pageon Sophie Victoria Pageon Katharina eGaus Katharina eGaus Jeremie eRossy Jeremie eRossy |
author_sort |
Natasha eKapoor-Kaushik |
title |
Distinct mechanisms regulate Lck spatial organization in activated T cells |
title_short |
Distinct mechanisms regulate Lck spatial organization in activated T cells |
title_full |
Distinct mechanisms regulate Lck spatial organization in activated T cells |
title_fullStr |
Distinct mechanisms regulate Lck spatial organization in activated T cells |
title_full_unstemmed |
Distinct mechanisms regulate Lck spatial organization in activated T cells |
title_sort |
distinct mechanisms regulate lck spatial organization in activated t cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2016-03-01 |
description |
Phosphorylation of the T cell receptor (TCR) by the kinase Lck is the first detectable signaling event upon antigen engagement. The distribution of Lck within the plasma membrane, its conformational state, kinase activity and protein interactions all contribute to determine how efficiently Lck phosphorylates the engaged TCR. Here we used cross-correlation raster image spectroscopy (ccRICS) and photoactivated localization microscopy (PALM) to identify two mechanisms of Lck clustering: an intrinsic mechanism of Lck clustering induced by locking Lck in its open conformation, and an extrinsic mechanism of clustering controlled by the phosphorylation of tyrosine 192, which regulates the affinity of Lck SH2 domain. Both mechanisms of clustering were differently affected by the absence of the kinase Zap70 or the adaptor Lat. We further observed that the adaptor TSAd bound to and promoted the diffusion of Lck when it is phosphorylated on tyrosine 192. Our data suggest that while Lck open conformation drives aggregation and clustering, the spatial organization of Lck is further controlled by signaling events downstream of TCR phosphorylation. |
topic |
Lck T cell signaling Membrane organization image correlation spectroscopy Super-resolution fluorescence microscopy assembly of signaling complexes |
url |
http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00083/full |
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