title: Phase separation of signaling molecules promotes T cell receptor signal transduction.
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.
authors.affiliation: Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Su
authors.affiliation: Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Biophysics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jonathon A
authors.initials: JA
authors.lastname: Ditlev
authors.affiliation: Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.
authors.forename: Enfu
authors.initials: E
authors.lastname: Hui
authors.affiliation: Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Biophysics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Wenmin
authors.initials: W
authors.lastname: Xing
authors.affiliation: Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Biophysics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Sudeep
authors.initials: S
authors.lastname: Banjade
authors.affiliation: Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Okrut
authors.affiliation: HHMI Mass Spectrometry Laboratory and Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: King
authors.affiliation: Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Taunton
authors.affiliation: Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Biophysics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ron.vale@ucsf.edu michael.rosen@utsouthwestern.edu.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Rosen
authors.affiliation: Howard Hughes Medical Institute (HHMI) Summer Institute, Marine Biological Laboratory, Woods Hole, MA 02543, USA. Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA. ron.vale@ucsf.edu michael.rosen@utsouthwestern.edu.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Vale
mesh_terms: D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases; D010766:Phosphorylation; D058105:Polymerization; D011948:Receptors, Antigen, T-Cell / Q000819:agonists*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C110810:LAT protein, human; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D020929:Mitogen-Activated Protein Kinase Kinases