King David S.

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David S.

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  • Preprint
    Phase separation of signaling molecules promotes T cell receptor signal transduction
    ( 2016-03) Su, Xiaolei ; Ditlev, Jonathon ; Hui, Enfu ; Xing, Wenmin ; Banjade, Sudeep ; Okrut, Julia ; King, David S. ; Taunton, Jack ; Rosen, Michael K. ; Vale, Ronald D.
    Activation of various cell surface receptors triggers the reorganization of downstream signaling molecules into micron- or submicron-sized clusters. However, the functional consequences of such clustering has been unclear. We biochemically reconstituted a 12-component signaling pathway on model membranes, beginning with T cell receptor (TCR) activation and ending with actin assembly. When TCR phoshophorylation was triggered, downstream signaling proteins spontaneously separated into liquid-like clusters that promoted signaling outputs both in vitro and in human Jurkat T cells. Reconstituted clusters were enriched in kinases but excluded phosphatases, and enhanced actin filament assembly by recruiting and organizing actin regulators. These results demonstrate that protein phase separation can create a distinct physical and biochemical compartment that facilitates signaling.