Publication Date:
2022-05-26
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.
Description:
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:
This work was supported by the HCIA
program of HHMI, the NIH (R01-GM56322 to M.K.R.) and Welch Foundation (I–1544 to
M.K.R.). X.S. was supported by CRI Irvington postdoctoral fellowship. J.A.D. was supported by
NRSA F32 award 5-F32-DK101188. E.H. was supported as a fellow of the Leukemia and
Lymphoma Society. J.O. was supported by funds from Tobacco-Related Disease Research
Program of the University of California (19FT-0090).
Description:
2016-10-07
Repository Name:
Woods Hole Open Access Server
Type:
Preprint
