TY - JOUR
T1 - SNX17 affects T cell activation by regulating TCR and integrin recycling
AU - Osborne, Douglas G.
AU - Piotrowski, Joshua T.
AU - Dick, Christopher J.
AU - Zhang, Jin San
AU - Billadeau, Daniel D.
N1 - Publisher Copyright:
Copyright © 2015 by The American Association of Immunologists, Inc.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - A key component in T cell activation is the endosomal recycling of receptors to the cell surface, thereby allowing continual integration of signaling and Ag recognition. One protein potentially involved in TCR transport is sorting nexin 17 (SNX17). SNX proteins have been found to bind proteins involved in T cell activation, but specifically the role of SNX17 in receptor recycling and T cell activation is unknown. Using immunofluorescence, we find that SNX17 colocalizes with TCR and localizes to the immune synapse in T-conjugates. Significantly, knockdown of the SNX17 resulted in fewer T-APC conjugates, lower CD69, TCR, and LFA-1 surface expression, as well as lower overall TCR recycling compared with control T cells. Lastly, we identified the 4.1/ezrin/radixin/moesin domain of SNX17 as being responsible in the binding and trafficking of TCR and LFA-1 to the cell surface. These data suggest that SNX17 plays a role in the maintenance of normal surface levels of activating receptors and integrins to permit optimum T cell activation at the immune synapse.
AB - A key component in T cell activation is the endosomal recycling of receptors to the cell surface, thereby allowing continual integration of signaling and Ag recognition. One protein potentially involved in TCR transport is sorting nexin 17 (SNX17). SNX proteins have been found to bind proteins involved in T cell activation, but specifically the role of SNX17 in receptor recycling and T cell activation is unknown. Using immunofluorescence, we find that SNX17 colocalizes with TCR and localizes to the immune synapse in T-conjugates. Significantly, knockdown of the SNX17 resulted in fewer T-APC conjugates, lower CD69, TCR, and LFA-1 surface expression, as well as lower overall TCR recycling compared with control T cells. Lastly, we identified the 4.1/ezrin/radixin/moesin domain of SNX17 as being responsible in the binding and trafficking of TCR and LFA-1 to the cell surface. These data suggest that SNX17 plays a role in the maintenance of normal surface levels of activating receptors and integrins to permit optimum T cell activation at the immune synapse.
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U2 - 10.4049/jimmunol.1402734
DO - 10.4049/jimmunol.1402734
M3 - Article
C2 - 25825439
AN - SCOPUS:84928491993
SN - 0022-1767
VL - 194
SP - 4555
EP - 4566
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -