Visualizing signaling output from the LAT protein condensate during T cell activation at the single molecule level

 Professor Jay T. Groves, Department of Chemistry, University of California Berkeley

 Linker for Activation of T cells (LAT) is an intrinsically disordered, membrane-anchored protein that serves as a scaffold to assemble key downstream signaling molecules in the T cell receptor pathway.  In reconstituted experiments, it has been recently demonstrated that the activation process of LAT involves a protein condensation phase transition^1,2, and this may further control downstream signaling activity³.  In this presentation, I will describe a series of single molecule imaging experiments performed in live T cells^4,5 aimed at visualizing the LAT phase transition and resolving how distinctive features of the phase transition (as opposed to a more linear assembly process) may contribute functional advantages to the T cell signaling system.  I will specifically present new data illustrating that calcium spiking and fluctuation activity in T cells can be traced to discrete, stochastic LAT condensation events.  I will also examine how this signal gating function of the LAT condensate enables T cells to be sensitive to single antigen pMHC molecules.

References 

            [1]  Su, …, and Vale, Science (2016) 352: p595
            [2]  Huang, …, and Groves, PNAS (2016) 113: p8218
            [3]  Huang, …, and Groves, Science (2019) 363: p1098
            [4]  Lin, …, and Groves, Science Sig. (2019) 12: eaat8715
            [5]  McAffee, … and Groves, Nature Comm. (2022) 13: p1