Publication Date:
2016-04-09
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Su, Xiaolei -- Ditlev, Jonathon A -- Hui, Enfu -- Xing, Wenmin -- Banjade, Sudeep -- Okrut, Julia -- King, David S -- Taunton, Jack -- Rosen, Michael K -- Vale, Ronald D -- 5-F32-DK101188/DK/NIDDK NIH HHS/ -- F32 DK101188/DK/NIDDK NIH HHS/ -- R01 GM056322/GM/NIGMS NIH HHS/ -- R01-GM56322/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):595-9. doi: 10.1126/science.aad9964. Epub 2016 Apr 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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. ; 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. ; HHMI Mass Spectrometry Laboratory and Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720, USA. ; 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. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27056844" target="_blank"〉PubMed〈/a〉
Keywords:
Actins/*metabolism
;
Adaptor Proteins, Signal Transducing/*metabolism
;
Fluorescence Recovery After Photobleaching
;
Humans
;
Jurkat Cells
;
Membrane Proteins/*metabolism
;
Mitogen-Activated Protein Kinase Kinases
;
Phosphorylation
;
Polymerization
;
Receptors, Antigen, T-Cell/*agonists
;
Signal Transduction
;
T-Lymphocytes/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
