Step-Wise Assembly of LAT Signaling Clusters Immediately After T Cell Receptor Triggering Contributes to Signal Propagation
Year: 2025
Type: article
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.
DOI: 10.3390/ijms26094076
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: The Plasma membrane in health and disease, Connecting the dots: Image analysis for single molecule localisation microscopy, Spatial organization of T cell signalling, ARC Centre of Excellence in Advanced Molecular Imaging, G4209227257, Regulation of the signalling efficiency of the T cell antigen receptor
OpenAlex ID: W4409814444