RT Journal Article
SR Electronic
T1 A Composition-Dependent Molecular Clutch Between T Cell Signaling Clusters and Actin
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 316414
DO 10.1101/316414
A1 Jonathon A. Ditlev
A1 Anthony R. Vega
A1 Darius V. Köster
A1 Xiaolei Su
A1 Ashley M. Lakoduk
A1 Ronald D. Vale
A1 Satyajit Mayor
A1 Khuloud Jaqaman
A1 Michael K. Rosen
YR 2018
UL http://biorxiv.org/content/early/2018/05/07/316414.abstract
AB 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.One-sentence summary Compositional changes alter T cell signaling cluster binding to actin, enabling cluster propulsion by distinct actin networks.