Tensin3 interaction with talin drives the formation of fibronectin-associated fibrillar adhesions

Paul Atherton, Rafaella Konstantinou, Suat Peng Neo, Emily Wang, Eleonora Balloi, Marina Ptushkina, Hayley Bennett, Kath Clark, Jayantha Gunaratne, David Critchley, Igor Barsukov, Edward Manser, Christoph Ballestrem

Research output: Contribution to journalArticlepeer-review

Abstract

The formation of healthy tissue involves continuous remodeling of the extracellular matrix (ECM). Whilst it is known that this requires integrin-associated cell-ECM adhesion sites (CMAs) and actomyosin-mediated forces, the underlying mechanisms remain unclear. Here, we examine how tensin3 contributes to the formation of fibrillar adhesions (FBs) and fibronectin fibrillogenesis. Using BioID mass spectrometry and a mitochondrial targeting assay, we establish that tensin3 associates with the mechanosensors such as talin and vinculin. We show that the talin R11 rod domain binds directly to a helical motif within the central intrinsically disordered region (IDR) of tensin3, whilst vinculin binds indirectly to tensin3 via talin. Using CRISPR knock-out cells in combination with defined tensin3 mutations, we show (i) that tensin3 is critical for the formation of α5β1-integrin FBs and for fibronectin fibrillogenesis, and (ii) the talin/tensin3 interaction drives this process, with vinculin acting to potentiate it.

Original languageEnglish
Article numbere202107022
JournalJournal of Cell Biology
Volume221
Issue number10
DOIs
Publication statusPublished - 3 Oct 2022

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