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

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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

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