Phase separation of signaling molecules promotes T cell receptor signal transduction
Phase separation of signaling molecules promotes T cell receptor signal transduction
Date
2016-03
Authors
Su, Xiaolei
Ditlev, Jonathon
Hui, Enfu
Xing, Wenmin
Banjade, Sudeep
Okrut, Julia
King, David S.
Taunton, Jack
Rosen, Michael K.
Vale, Ronald D.
Ditlev, Jonathon
Hui, Enfu
Xing, Wenmin
Banjade, Sudeep
Okrut, Julia
King, David S.
Taunton, Jack
Rosen, Michael K.
Vale, Ronald D.
Linked Authors
Person
Person
Person
Person
Person
Alternative Title
Citable URI
As Published
Date Created
Location
DOI
Related Materials
Replaces
Replaced By
Keywords
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 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.
Description
Author Posting. © The Author(s), 2016. This is the author's version of the work. It is posted here by permission of American Association for the Advancement of Science for personal use, not for redistribution. The definitive version was published in Science 352 (2016): 595-599, doi:10.1126/science.aad9964.