Talin-tensin3 interactions regulate fibrillar adhesion formation and tensin3 phase separation.

Li, Xingchen ORCID: 0000-0003-2027-3770, Konstantinou, Rafaella ORCID: 0000-0003-0017-7300, Meena, Vinod Kumar ORCID: 0000-0002-1175-5631, Notash, Saba ORCID: 0009-0005-8691-2901, Khalil, Komal ORCID: 0000-0001-9809-417X, Whalley, Tom ORCID: 0009-0002-6852-9560, Atherton, Paul ORCID: 0000-0003-3098-674X, Barsukov, Igor ORCID: 0000-0003-4406-9803, Zacharchenko, Thomas ORCID: 0000-0001-5621-8605 and Ballestrem, Christoph ORCID: 0000-0002-5375-7985 (2026) Talin-tensin3 interactions regulate fibrillar adhesion formation and tensin3 phase separation. The Journal of cell biology, 225 (1). e202503155-. ISSN 0021-9525, 1540-8140

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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.

Item Type:	Article
Uncontrolled Keywords:	Extracellular Matrix, Animals, Humans, Mice, Talin, Fibronectins, Cell Adhesion, Protein Binding, Tensins, Phase Separation
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology (T&R Staff) Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Molecular & Clinical Cancer Medicine Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Biochemistry, Cell and Systems Biology
Depositing User:	Symplectic Admin
Date Deposited:	08 Dec 2025 09:30
Last Modified:	08 Dec 2025 09:30
DOI:	10.1083/jcb.202503155
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3195913
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