A composition-dependent molecular clutch between T cell signaling condensates and actin
Year: 2019
Type: article
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.
Source: eLife
DOI: 10.7554/elife.42695
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: Howard Hughes Medical Institute, Cancer Research Institute, Welch Foundation, Cancer Prevention and Research Institute of Texas, University of Texas Southwestern Medical Center, Wellcome Trust, Department of Science and Technology, Ministry of Science and Technology, India, AXA Research Fund, The Wellcome Trust DBT India Alliance, National Institutes of Health, Japan Society for the Promotion of Science, National Centre for Biological Sciences, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1611016065, G245217697, Development of 3D molecular orientation imaging and its application to cellular architectural dynamics, Fluorescent single molecule orientation imaging in living cells, Mechanisms and functional consequences of compositional regulation at the local and global scale in membranes of living cells, G5163488259, G6528762291, Cancer Intervention and Prevention Discoveries Program, G815927962, G8185087191, Recruitment of First-Time, Tenure-Track Faculty Members, G9000329322, G9000344378, Mechanisms and Functional Consequences of Signaling Protein Organization at Membranes
OpenAlex ID: W2956058000