(
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.