Phase separation of signaling molecules promotes T cell receptor signal transduction

Xiaolei Su, Jonathon A. Ditlev, Enfu Hui, Wenmin Xing, Sudeep Banjade, Julia Okrut, David S. King, Jack Taunton, Michael K. Rosen, Ronald D. Vale

Research output: Contribution to journalArticle

232 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)595-599
Number of pages5
JournalScience
Volume352
Issue number6285
DOIs
StatePublished - Apr 29 2016

ASJC Scopus subject areas

  • General

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    Su, X., A. Ditlev, J., Hui, E., Xing, W., Banjade, S., Okrut, J., King, D. S., Taunton, J., Rosen, M. K., & Vale, R. D. (2016). Phase separation of signaling molecules promotes T cell receptor signal transduction. Science, 352(6285), 595-599. https://doi.org/10.1126/science.aad9964