A Composition-Dependent Molecular Clutch Between T Cell Signaling Clusters and Actin

During T cell activation, phase-separated signaling protein clusters are moved toward the center of the immunological synapse by two distinct, concentric actin networks. How clusters move with actin is unknown. We observed that clusters lose the adaptor protein Nck as the clusters move across the boundary of the two actin networks. Biochemically reconstituted clusters with weak actin binders, Nck and its ligand N-WASP, promoted the strong association and movement of clusters with mobile actomyosin filaments. Clusters lacking these components were instead propelled by mechanical interactions. Basic elements of Nck and N-WASP coupled clusters to actin in vitro, and clusters constitutively containing basic elements moved aberrantly in cells. We propose that Nck and N-WASP act as a clutch between clusters and actin, and that changes in composition of these condensates enable cluster movement by the distinct dynamics of actin networks in different regions of the immunological synapse.