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

Jonathon A. Ditlev, Anthony R. Vega, Darius Vasco Köster, Xiaolei Su, Tomomi Tani, Ashley M. Lakoduk, Ronald D. Vale, Satyajit Mayor, Khuloud Jaqaman, Michael K Rosen

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Jul 3 2019

Fingerprint

Cell signaling
T-cells
Clutches
Actins
T-Lymphocytes
Immunological Synapses
Chemical analysis
Phase separation
Actomyosin
Adhesion
Chemical activation
Association reactions

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

A composition-dependent molecular clutch between T cell signaling condensates and actin. / Ditlev, Jonathon A.; Vega, Anthony R.; Köster, Darius Vasco; Su, Xiaolei; Tani, Tomomi; Lakoduk, Ashley M.; Vale, Ronald D.; Mayor, Satyajit; Jaqaman, Khuloud; Rosen, Michael K.

In: eLife, Vol. 8, 03.07.2019.

Research output: Contribution to journalArticle

Ditlev, JA, Vega, AR, Köster, DV, Su, X, Tani, T, Lakoduk, AM, Vale, RD, Mayor, S, Jaqaman, K & Rosen, MK 2019, 'A composition-dependent molecular clutch between T cell signaling condensates and actin', eLife, vol. 8. https://doi.org/10.7554/eLife.42695
Ditlev, Jonathon A. ; Vega, Anthony R. ; Köster, Darius Vasco ; Su, Xiaolei ; Tani, Tomomi ; Lakoduk, Ashley M. ; Vale, Ronald D. ; Mayor, Satyajit ; Jaqaman, Khuloud ; Rosen, Michael K. / A composition-dependent molecular clutch between T cell signaling condensates and actin. In: eLife. 2019 ; Vol. 8.
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AU - Tani, Tomomi

AU - Lakoduk, Ashley M.

AU - Vale, Ronald D.

AU - Mayor, Satyajit

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AU - Rosen, Michael K

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