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Phase separation of signaling molecules promotes T cell receptor signal transduction.

ABSTRACT: 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.

SUBMITTER: Su X

PROVIDER: S-EPMC4892427 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Phase separation of signaling molecules promotes T cell receptor signal transduction.

Su Xiaolei X Ditlev Jonathon A JA Hui Enfu E Xing Wenmin W Banjade Sudeep S Okrut Julia J King David S DS Taunton Jack J Rosen Michael K MK Vale Ronald D RD

Science (New York, N.Y.) 20160407 6285

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 liqui ...[more]

PMID: 27056844

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