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bioRxiv · 10.1101/2021.07.16.452612

Tensin3 interaction with talin drives formationof fibronectin-associated fibrillar adhesions

Atherton, P.·Konstantinou, R.·Neo, S. P.·Wang, E.·Balloi, E.·Ptushkina, M.·Bennett, H.·Clark, K.·Gunaratne, J.·Critchley, D.·Barsukov, I.·Manser, E.·Ballestrem, C.
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Abstract

The formation of healthy tissue involves continuous remodelling 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 formation of fibrillar adhesions (FBs) and fibronectin fibrillo-genesis. Using BioID mass spectrometry and a mitochondrial targeting assay, we establish that tensin3 associates with the mechanosensors 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 formation of 5{beta}1-integrin FBs and for fibronectin fibrillogenesis, and (ii) the talin/tensin3 interaction drives this process, with vinculin acting to potentiate it.

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Atherton, P., Konstantinou, R., Neo, S. P., Wang, E., Balloi, E., Ptushkina, M., Bennett, H., Clark, K., Gunaratne, J., Critchley, D., Barsukov, I., Manser, E., Ballestrem, C.. 2021-07-16. Tensin3 interaction with talin drives formationof fibronectin-associated fibrillar adhesions. https://doi.org/10.1101/2021.07.16.452612

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