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

191 Citations (Scopus)

Abstract

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 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)1-8
Number of pages8
JournalScience
DOIs
StateAccepted/In press - Apr 7 2016

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T-Cell Antigen Receptor
Actins
Signal Transduction
Jurkat Cells
Cell Surface Receptors
Actin Cytoskeleton
Phosphoric Monoester Hydrolases
Cluster Analysis
Proteins
Phosphotransferases
Phosphorylation
T-Lymphocytes
Membranes
In Vitro Techniques

ASJC Scopus subject areas

  • General

Cite this

Su, X., A. Ditlev, J., Hui, E., Xing, W., Banjade, S., Okrut, J., ... Vale, R. D. (Accepted/In press). Phase separation of signaling molecules promotes T cell receptor signal transduction. Science, 1-8. https://doi.org/10.1126/science.aad9964

Phase separation of signaling molecules promotes T cell receptor signal transduction. / Su, Xiaolei; A. Ditlev, Jonathon; Hui, Enfu; Xing, Wenmin; Banjade, Sudeep; Okrut, Julia; King, David S.; Taunton, Jack; Rosen, Michael K.; Vale, Ronald D.

In: Science, 07.04.2016, p. 1-8.

Research output: Contribution to journalArticle

Su, X, A. Ditlev, J, Hui, E, Xing, W, Banjade, S, Okrut, J, King, DS, Taunton, J, Rosen, MK & Vale, RD 2016, 'Phase separation of signaling molecules promotes T cell receptor signal transduction', Science, pp. 1-8. https://doi.org/10.1126/science.aad9964
Su, Xiaolei ; A. Ditlev, Jonathon ; Hui, Enfu ; Xing, Wenmin ; Banjade, Sudeep ; Okrut, Julia ; King, David S. ; Taunton, Jack ; Rosen, Michael K. ; Vale, Ronald D. / Phase separation of signaling molecules promotes T cell receptor signal transduction. In: Science. 2016 ; pp. 1-8.
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