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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2018.02655

Phosphatase of regenerating liver-1 (PRL-1) regulates actin dynamics during Immunological Synapse assembly and T cell effector function

  • 1Departamento de Microbiología, Universidad Complutense de Madrid, Spain
  • 2Servicio de Inmunología, Hospital de la Princesa, Spain
  • 3Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Spain
  • 4Institute of Molecular and Cell Biology (A*STAR), Singapore
  • 5Complutense University of Madrid, Spain

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.

Keywords: T-cell immune response, Immunological Synapse, Phosphates of Regenerating liver, Actin Cytoskeleton, IL-2

Received: 12 Aug 2018; Accepted: 29 Oct 2018.

Edited by:

Bernard Malissen, INSERM U1104 Centre d'immunologie de Marseille-Luminy, France

Reviewed by:

Cosima T. Baldari, Università degli Studi di Siena, Italy
Christoph Wülfing, University of Bristol, United Kingdom  

Copyright: © 2018 Castro-Sanchez, Ramirez-Munoz, Martin-Cofreces, Aguilar-Sopena, Alegre-Gomez, Hernandez-Perez, Reyes, Zeng, Cabañas, Sanchez-Madrid and Roda-Navarro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Pedro Roda-Navarro, Complutense University of Madrid, Madrid, Spain, proda@med.ucm.es