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Elife. 2019 Jul 3;8. pii: e42695. doi: 10.7554/eLife.42695.

A composition-dependent molecular clutch between T cell signaling condensates and actin.

Author information

1
Howard Hughes Medical Institute, Summer Institute, Marine Biological Laboratory, Woods Hole, United States.
2
Department of Biophysics, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States.
3
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States.
4
National Centre for Biological Sciences, Tata Institute for Fundamental Research, Bangalore, India.
5
Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
6
Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological Laboratory, Woods Hole, United States.
7
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States.
8
Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, United States.
#
Contributed equally

Abstract

During T cell activation, biomolecular condensates form at the immunological synapse (IS) through multivalency-driven phase separation of LAT, Grb2, Sos1, SLP-76, Nck, and WASP. These condensates move radially at the IS, traversing successive radially-oriented and concentric actin networks. To understand this movement, we biochemically reconstituted LAT condensates with actomyosin filaments. We found that basic regions of Nck and N-WASP/WASP promote association and co-movement of LAT condensates with actin, indicating conversion of weak individual affinities to high collective affinity upon phase separation. Condensates lacking these components were propelled differently, without strong actin adhesion. In cells, LAT condensates lost Nck as radial actin transitioned to the concentric network, and engineered condensates constitutively binding actin moved aberrantly. Our data show that Nck and WASP form a clutch between LAT condensates and actin in vitro and suggest that compositional changes may enable condensate movement by distinct actin networks in different regions of the IS.

KEYWORDS:

LAT microclusters; T cell signaling; actin cytoskeleton; biochemical reconstitution; biochemistry; biomolecular condensate; cell biology; chemical biology; compositional control; human

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