QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online March 2, 2004
doi: 10.1242/10.1242/jcs.00968

This Article Figures Only Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bonello, G. Articles by Collette, Y. Search for Related Content PubMed PubMed Citation Articles by Bonello, G. Articles by Collette, Y. Social Bookmarking                         What's this?

Dynamic recruitment of the adaptor protein LAT: LAT exists in two distinct intracellular pools and controls its own recruitment

Grégory Bonello^1,*, Nicolas Blanchard^2,*, Maria C. Montoya³, Enrique Aguado⁴, Claire Langlet⁴, Hai-Tao He⁴, Selena Nunez-Cruz⁴, Marie Malissen⁴, Francisco Sanchez-Madrid³, Daniel Olive¹, Claire Hivroz^2,*, and Yves Collette^1,*,,

¹ Institut de Cancérologie et d'Immunologie de Marseille, Université de la Méditerranée, INSERM, Unite 119, Marseille, France
² Institut National de la Santé et de la Recherche Médicale, Unite 520, Institut Curie, Paris, France
³ Servicio de Immunologia, Hospital de la Princesa, Universidad Autonoma de Madrid, Madrid, Spain
⁴ Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Université de la Méditerranée, Marseille, France

Author for correspondence (e-mail: collette{at}marseille.inserm.fr)

Accepted 4 November 2003

The integral membrane adaptor protein linker for activation of T cells (LAT) couples the T-cell receptor (TCR) with downstream signalling and is essential for T-cell development and activation. Here, we investigate the dynamic distribution of LAT-GFP fusion proteins by time-lapse video imaging of live T lymphocytes interacting with antigen-presenting cells. We show that LAT forms two distinct cellular pools, one at the plasma membrane and one that co-distributes with transferrin-labelled intracellular compartments also containing the TCR/CD3-associated chain. The distribution of LAT between these two pools is dependent on LAT intracytoplasmic residues. Whereas plasma membrane-associated LAT is recruited to immune synapses after a few seconds of cell conjugate formation, the intracellular pool is first polarized and then recruited after a few minutes. We further show that LAT intracytoplasmic amino acid residues, particularly the Tyr136, 175, 195 and 235 residues, are required for its own recruitment to the immune synapse and that a herein-identified juxtamembrane LAT region (amino acids 32-104) is involved in the localization of LAT in intracellular pools and in T-cell signalling. Altogether, our results demonstrate that LAT controls its own recruitment at the immune synapse, where it is required as a scaffold protein for the signalling machinery. The results also suggest that the intracellular pool of LAT might be required for T-cell activation.

Key words: T-cell signalling, LAT, Raft, Immune synapse, Video imaging, Endosomes

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. G. Marko, H.-J. E. Pang, Z. Ren, A. Azzi, B. T. Huber, S. C. Bunnell, and S. N. Meydani Vitamin E Reverses Impaired Linker for Activation of T Cells Activation in T Cells from Aged C57BL/6 Mice J. Nutr., June 1, 2009; 139(6): 1192 - 1197. [Abstract] [Full Text] [PDF]

				O. Anton, A. Batista, J. Millan, L. Andres-Delgado, R. Puertollano, I. Correas, and M. A. Alonso An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes J. Exp. Med., December 22, 2008; 205(13): 3201 - 3213. [Abstract] [Full Text] [PDF]

				N. B. Martin-Cofreces, J. Robles-Valero, J. R. Cabrero, M. Mittelbrunn, M. Gordon-Alonso, C.-H. Sung, B. Alarcon, J. Vazquez, and F. Sanchez-Madrid MTOC translocation modulates IS formation and controls sustained T cell signaling J. Cell Biol., September 9, 2008; 182(5): 951 - 962. [Abstract] [Full Text] [PDF]

				L. Balagopalan, V. A. Barr, C. L. Sommers, M. Barda-Saad, A. Goyal, M. S. Isakowitz, and L. E. Samelson c-Cbl-Mediated Regulation of LAT-Nucleated Signaling Complexes Mol. Cell. Biol., December 15, 2007; 27(24): 8622 - 8636. [Abstract] [Full Text] [PDF]

				M. Wu, T. Baumgart, S. Hammond, D. Holowka, and B. Baird Differential targeting of secretory lysosomes and recycling endosomes in mast cells revealed by patterned antigen arrays J. Cell Sci., September 1, 2007; 120(17): 3147 - 3154. [Abstract] [Full Text] [PDF]

				C. M. Mutch, R. Sanyal, T. L. Unruh, L. Grigoriou, M. Zhu, W. Zhang, and J. P. Deans Activation-induced endocytosis of the raft-associated transmembrane adaptor protein LAB/NTAL in B lymphocytes: evidence for a role in internalization of the B cell receptor Int. Immunol., January 1, 2007; 19(1): 19 - 30. [Abstract] [Full Text] [PDF]

				E. F. Corbett-Nelson, D. Mason, J. G. Marshall, Y. Collette, and S. Grinstein Signaling-dependent immobilization of acylated proteins in the inner monolayer of the plasma membrane J. Cell Biol., July 17, 2006; 174(2): 255 - 265. [Abstract] [Full Text] [PDF]

				N. B. Martin-Cofreces, D. Sancho, E. Fernandez, M. Vicente-Manzanares, M. Gordon-Alonso, M. C. Montoya, F. Michel, O. Acuto, B. Alarcon, and F. Sanchez-Madrid Role of Fyn in the Rearrangement of Tubulin Cytoskeleton Induced through TCR J. Immunol., April 1, 2006; 176(7): 4201 - 4207. [Abstract] [Full Text] [PDF]

				S. E. Ziemba, R. R. Mattingly, M. J. McCabe Jr., and A. J. Rosenspire Inorganic Mercury Inhibits the Activation of LAT in T-Cell Receptor-Mediated Signal Transduction Toxicol. Sci., January 1, 2006; 89(1): 145 - 153. [Abstract] [Full Text] [PDF]