Phase separation of signaling molecules promotes T cell receptor signal transduction
King, David S.
Rosen, Michael K.
Vale, Ronald D.
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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.
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.
Suggested CitationPreprint: Su, Xiaolei, 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", 2016-03, https://doi.org/10.1126/science.aad9964, https://hdl.handle.net/1912/8156
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