Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions

• Published in: The Journal of cell biology Vol. 217; no. 6; pp. 1929 - 1940
• Main Authors: Spiess, Matthias, Hernandez-Varas, Pablo, Oddone, Anna, Olofsson, Helene, Blom, Hans, Waithe, Dominic, Lock, John G, Lakadamyali, Melike, Strömblad, Staffan
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 04-06-2018
• Subjects: Cell Line, Tumor; Cytoskeletal Proteins - metabolism; Focal Adhesions - metabolism; Humans; Integrin beta1 - metabolism; Medicin och hälsovetenskap; Protein Transport; Talin - metabolism; Vinculin - metabolism
• ISSN: 0021-9525; 1540-8140; 1540-8140
• DOI: 10.1083/jcb.201707075

Integrins are the core constituents of cell-matrix adhesion complexes such as focal adhesions (FAs) and play key roles in physiology and disease. Integrins fluctuate between active and inactive conformations, yet whether the activity state influences the spatial organization of integrins within FAs has remained unclear. In this study, we address this question and also ask whether integrin activity may be regulated either independently for each integrin molecule or through locally coordinated mechanisms. We used two distinct superresolution microscopy techniques, stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion microscopy (STED), to visualize active versus inactive β1 integrins. We first reveal a spatial hierarchy of integrin organization with integrin molecules arranged in nanoclusters, which align to form linear substructures that in turn build FAs. Remarkably, within FAs, active and inactive β1 integrins segregate into distinct nanoclusters, with active integrin nanoclusters being more organized. This unexpected segregation indicates synchronization of integrin activities within nanoclusters, implying the existence of a coordinate mechanism of integrin activity regulation.