Step-Wise Assembly of LAT Signaling Clusters Immediately After T Cell Receptor Triggering Contributes to Signal Propagation

TL;DR

This study shows how LAT proteins assemble in the cell membrane after T cell receptor activation, helping to spread signals important for immune responses.

Contribution

The study reveals a step-wise assembly mechanism of LAT signaling clusters that facilitates signal propagation after TCR triggering.

Findings

LAT molecules assemble into immobile signaling entities in the plasma membrane after TCR engagement.

The assembly process is coordinated via the Zap70-LAT-Grb2 signaling pathway.

De novo plasma membrane assemblies contribute to signal propagation.

Abstract

Linker for activation of T cells (LAT) is an essential adaptor protein in early T cell receptor (TCR) signaling that propagates multiple signaling pathways. However, how LAT spatial organization facilitates signal initiation and propagation after TCR triggering is not clear. To differentiate de novo assembly in the plasma membrane from pre-existing LAT vesicles and clusters, we developed imaging protocols and analyses to capture the organization and dynamics of single LAT molecules immediately after TCR engagement. We could observe individual LAT molecules in the plasma membrane that assembled into immobile signaling entities requiring LAT phosphorylation. This step-wise assembly process was temporally highly coordinated via the zeta-chain-associated protein kinase 70 (Zap70)-LAT-growth factor receptor-bound protein 2 (Grb2) pathway. While multiple spatial organization co-existed even within the plasma membrane, our data suggest that de novo plasma membrane assemblies facilitated signal propagation.

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