Phosphatase of Regenerating Liver-1 (PRL-1) Regulates Actin Dynamics During Immunological Synapse Assembly and T Cell Effector Function

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Phosphatase of Regenerating Liver-1 (PRL-1) Regulates Actin Dynamics During Immunological Synapse Assembly and T Cell Effector Function
Title:
Phosphatase of Regenerating Liver-1 (PRL-1) Regulates Actin Dynamics During Immunological Synapse Assembly and T Cell Effector Function
Journal Title:
Frontiers in Immunology
Keywords:
Publication Date:
20 November 2018
Citation:
Castro-Sánchez P, Ramirez-Munoz R, Martín-Cófreces NB, Aguilar-Sopeña O, Alegre-Gomez S, Hernández-Pérez S, Reyes R, Zeng Q, Cabañas C, Sánchez-Madrid F and Roda-Navarro P (2018) Phosphatase of Regenerating Liver-1 (PRL-1) Regulates Actin Dynamics During Immunological Synapse Assembly and T Cell Effector Function. Front. Immunol. 9:2655. doi: 10.3389/fimmu.2018.02655
Abstract:
The regulatory role of most dual specific phosphatases during T cell activation remains unknown. Here, we have studied the expression and function of phosphatases of regenerating liver (PRLs: PRL-1, PRL-2, and PRL-3) during T cell activation, as well as, the dynamic delivery of PRL-1 to the Immunological Synapse (IS). We found that T cell activation downregulates the expression of PRL-2, resulting in an increased PRL-1/PRL-2 ratio. PRL-1 redistributed at the IS in two stages: Initially, it was transiently accumulated at scanning membranes enriched in CD3 and actin, and at later times, it was delivered at the contact site from pericentriolar, CD3ζ-containing, vesicles. Once at the established IS, PRL-1 distributed to LFA-1 and CD3ε sites. Remarkably, PRL-1 was found to regulate actin dynamics during IS assembly and the secretion of IL-2. Moreover, pharmacological inhibition of the catalytic activity of the three PRLs reduced the secretion of IL-2. These results provide evidence indicating a regulatory role of PRL-1 during IS assembly and highlight the involvement of PRLs in immune responses by mature T cells.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
PR-N and the students PC-S and RR-M are founded by European Union (Career reintegration grant, FP7-PEOPLE-2012-CIG-321858) and the Ministry of Economy and Competitiveness (MINECO) with research grants SAF2012-33218 and SAF2016-75656-P. The later from the Agencia Estatal de investigación cofounded by “fondo Europeo de desarrollo regional (FEDER)”.
Description:
ISSN:
1664-3224
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