Talin–tensin3 interactions regulate fibrillar adhesion formation and tensin3 phase separation
Year: 2025
Type: article
Abstract: Integrin-mediated cell-matrix adhesions regulate communication between cells and the extracellular matrix. In matrix-secreting cells, fibrillar adhesions (FBs) containing high levels of α5β1 integrins and the tensin3 adaptor protein are essential for fibronectin (FN) fibrillogenesis. Here, we demonstrate that tensin3 binds to four helical regions (R3, R4, R8, and R11) of talin, the principal integrin activator. Structural analysis revealed the residues critical for the tensin3-talin interaction, and mutational analysis showed that talin R8 and R11 are essential for FB formation and FN fibrillogenesis. Cellular experiments demonstrate that tensin3 binding to talin not only regulates integrin activation, but also modulates tensin3's propensity to undergo liquid-liquid phase separation (LLPS). Formation of such LLPS condensates increased when cells were plated on soft substrates compared with stiff ones. This effect was abolished by blocking the interaction between tensin3 and talin. Our data suggest a model in which LLPS condensates provide a signaling platform involved in cellular responses to sudden changes in tissue mechanics.
Source: The Journal of Cell Biology
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: EPSRC Centre for Doctoral Training in Advanced Biomedical Materials, How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs., How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs., G6222463922, Extension Request for Wellcome Centre for Cell-Matrix Research, Orchestration of adhesion signalling networks by the tensins and their impact in cell motility and matrix remodelling.
OpenAlex ID: W4416624786