TitleA composition-dependent molecular clutch between T cell signaling condensates and actin.
Publication TypeJournal Article
Year of Publication2019
AuthorsDitlev JA, Vega AR, Köster DVasco, Su X, Tani T, Lakoduk AM, Vale RD, Mayor S, Jaqaman K, Rosen MK
Date Published2019 Jul 03

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.

Alternate JournalElife
PubMed ID31268421
PubMed Central IDPMC6624021
Grant ListI-1544 / / Welch Foundation /
J C Bose Fellowship / / Department of Science and Technology, Ministry of Science and Technology /
Margadarshi Fellowship (IA/M/15/1/502018) / / Wellcome Trust/DBT India Alliance /
R01 GM100160 / / National Institutes of Health /
Endowed Scholars Program / / UT Southwestern /
National Research Service Award F32 (F32 DK101188) / / National Institutes of Health /
Training Grant RP140110 PI: Michael White / / Cancer Prevention and Research Institute of Texas /
R35 GM119619 / / National Institutes of Health /
F32 DK101188 / / National Institutes of Health /
R1216 / / Cancer Prevention and Research Institute of Texas /
J C Bose Fellowship / / Department of Science and Technology, Government of India /
IA/M/15/1/502018 / / Margadarshi Fellowship from the Wellcome Trust - Department of Biotechnology, India Alliance /
F32 DK101188 / / National Research Service Award F32 /
RP140110 PI: Michael White / / CPRIT Training Grant /