The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published online December 8, 2008
doi:10.1084/jem.20080552
The Journal of Experimental Medicine, Vol. 205, No. 13, 3201-3213
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Antón et al.
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ARTICLE

 An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes

Olga Antón1, Alicia Batista1, Jaime Millán1, Laura Andrés-Delgado1, Rosa Puertollano2, Isabel Correas1, and Miguel A. Alonso1

1 Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain
2 Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892

CORRESPONDENCE Miguel A. Alonso: maalonso{at}cbm.uam.es

The MAL protein is an essential component of the specialized machinery for apical targeting in epithelial cells. The src family kinase Lck plays a pivotal role in T cell signaling. We show that MAL is required in T cells for efficient expression of Lck at the plasma membrane and activation of IL-2 transcription. To investigate the mechanism by which MAL regulates Lck targeting, we analyzed the dynamics of Lck and found that it travels to the plasma membrane in specific transport carriers containing MAL. Coimmunoprecipitation experiments indicated an association of MAL with Lck. Both carrier formation and partitioning of Lck into detergent-insoluble membranes were ablated in the absence of MAL. Polarization of T cell receptor for antigen (TCR) and microtubule-organizing center to immunological synapse (IS) were also defective. Although partial correction of the latter defects was possible by forced expression of Lck at the plasma membrane, their complete correction, formation of transport vesicles, partitioning of Lck, and restoration of signaling pathways, which are required for IL-2 transcription up-regulation, were achieved by exogenous expression of MAL. We concluded that MAL is required for recruitment of Lck to specialized membranes and formation of specific transport carriers for Lck targeting. This novel transport pathway is crucial for TCR-mediated signaling and IS assembly.

Abbreviations used: IS, immunological synapse; JTIM, Jurkat TCR-signaling impaired mutant; mRNA, messenger RNA; MTOC, microtubule-organizing center; SEE, staphylococcal enterotoxin E; siRNA, short interfering RNA.

O. Antón and A. Batista contributed equally to this paper.

© 2008 Antón et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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