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A composition-dependent molecular clutch between T cell signaling condensates and actin
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Ditlev, Jonathon A., Vega, Anthony R., Köster, Darius Vasco, Su, Xiaolei, Tani, Tomomi, Lakoduk, Ashley M., Vale, Ronald D., Mayor, Satyajit, Jaqaman, Khuloud and Rosen, Michael K. (2019) A composition-dependent molecular clutch between T cell signaling condensates and actin. eLife, 8 . e42695 . doi:10.7554/eLife.42695 ISSN 2050-084X.
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WRAP-composition-dependent-molecular-clutch-cell-signalling-actin-Koster-2019.pdf - Accepted Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (43Mb) | Preview |
Official URL: http://dx.doi.org/10.7554/eLife.42695
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.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QP Physiology Q Science > QR Microbiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | T cells, T cells -- Receptors, Immune response -- Molecular aspects, Synapses, Antigen presenting cells | ||||||||||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | eLife | ||||||||||||||||||||||||||||||||||||||||||||||||
| Publisher: | eLife Sciences Publications Ltd. | ||||||||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 2050-084X | ||||||||||||||||||||||||||||||||||||||||||||||||
| Official Date: | 3 July 2019 | ||||||||||||||||||||||||||||||||||||||||||||||||
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| Volume: | 8 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Article Number: | e42695 | ||||||||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.7554/eLife.42695 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||||||||||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||||||||||||||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||||||||||||||||||||||||||
| Date of first compliant deposit: | 5 July 2019 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Date of first compliant Open Access: | 8 July 2019 | ||||||||||||||||||||||||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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