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[Report] Phase separation of signaling molecules promotes T cell receptor signal transduction

ScienceNOW - Fetched: April 28th, 2016, 5:00pm UTC

Activation of various cell surface receptors triggers the reorganization of downstream signaling molecules into micrometer- or submicrometer-sized clusters. However, the functional consequences of such clustering have 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 phosphorylation 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. Authors: Xiaolei Su, Jonathon A. Ditlev, Enfu Hui, Wenmin Xing, Sudeep Banjade, Julia Okrut, David S. King, Jack Taunton, Michael K. Rosen, Ronald D. Vale

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