RIAM and Vinculin Binding to Talin Are Mutually Exclusive and Regulate Adhesion Assembly and Turnover

Goult, Benjamin T.; Zacharchenko, Thomas; Bate, Neil; Tsang, Ricky; Hey, Fiona; Gingras, Alexandre R.; Elliott, P.R.; Roberts, G. C. K.; Ballestrem, Christoph; Critchley, David R.; Barsukov, Igor

doi:10.1074/jbc.m112.438119

Cited by 189 publications

(408 citation statements)

References 48 publications

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“…We have recently determined the boundaries and structures of the talin1 rod domains showing it contains 13 domains (R1–R13) 24 organised into two functionally distinct regions, a linear C‐terminal rod‐like region comprised of 5‐helix bundles and a compact N‐terminal region where three 4‐helix bundles (R2–R4) are inserted into the series of 5‐helix bundles (Fig. 2b).…”

Section: Structure Of Talin 1 Andmentioning

confidence: 99%

“…As force is exerted on talin, another layer of autoinhibition is uncovered (Bottom). As talin domains unfold, starting with R3, the initial mechanosensor in talin 21, 23, 24, vinculin‐binding sites are exposed and talin:vinculin interactions can now occur. R3 unfolding also reveals the high affinity actin‐binding site in talin, ABS 2 that can then activate tension‐bearing actin connections 84, 85.…”

Section: Talin1 and Talin2 Rod Interactionsmentioning

confidence: 99%

“…The initial mechanosensitive domain in talin has been shown to be R3 23, 24, which binds RIAM but also contains two VBS. However, vinculin and RIAM have fundamentally different modes of binding.…”

Section: The Mechanical Properties Of Talinmentioning

confidence: 99%

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The tale of two talins – two isoforms to fine‐tune integrin signalling

Gough

Goult

2018

FEBS Letters

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Talins are cytoplasmic adapter proteins essential for integrin‐mediated cell adhesion to the extracellular matrix. Talins control the activation state of integrins, link integrins to cytoskeletal actin, recruit numerous signalling molecules that mediate integrin signalling and coordinate recruitment of microtubules to adhesion sites via interaction with KANK (kidney ankyrin repeat‐containing) proteins. Vertebrates have two talin genes, TLN1 and TLN2. Although talin1 and talin2 share 76% protein sequence identity (88% similarity), they are not functionally redundant, and the differences between the two isoforms are not fully understood. In this Review, we focus on the similarities and differences between the two talins in terms of structure, biochemistry and function, which hint at subtle differences in fine‐tuning adhesion signalling.

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Section: Structure Of Talin 1 Andmentioning

confidence: 99%

Section: Talin1 and Talin2 Rod Interactionsmentioning

confidence: 99%

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The tale of two talins – two isoforms to fine‐tune integrin signalling

Gough

Goult

2018

FEBS Letters

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“…As a VBS consists of a single α-helix, many of the 62 α-helices of talin could be VBSs; indeed, an in vitro analysis identified ten strong VBSs and a further nine weaker ones . Binding sites have also been characterised for RIAM, paxillin, α-synemin, DLC1, Kank1 and Kank2 (Sun et al, 2008(Sun et al, , 2016Lee et al, 2009;Gingras et al, 2010;Li et al, 2011;Goult et al, 2013b;Bouchet et al, 2016;Zacharchenko et al, 2016). Furthermore, talin is required for recruitment of all IAPs examined to date in Drosophila (e.g.…”

Section: Introductionmentioning

confidence: 99%

Talin – the master of integrin adhesions

Klapholz

Brown

2017

Journal of Cell Science

263

222

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Talin has emerged as the key cytoplasmic protein that mediates integrin adhesion to the extracellular matrix. In this Review, we draw on experiments performed in mammalian cells in culture and Drosophila to present evidence that talin is the most important component of integrin adhesion complexes. We describe how the properties of this adaptor protein enable it to orchestrate integrin adhesions. Talin forms the core of integrin adhesion complexes by linking integrins directly to actin, increasing the affinity of integrin for ligands (integrin activation) and recruiting numerous proteins. It regulates the strength of integrin adhesion, senses matrix rigidity, increases focal adhesion size in response to force and serves as a platform for the building of the adhesion structure. Finally, the mechano-sensitive structure of talin provides a paradigm for how proteins transduce mechanical signals to chemical signals.

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“…Talin contains an N-terminal globular head domain and a C-terminal rod domain (Goult et al, 2013;Nuckolls et al, 1990). The talin head domain contains a FERM domain and is responsible for the binding of talin to β-integrin tails (Calderwood et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Talin2-mediated traction force drives matrix degradation and cell invasion

Jafari

et al. 2016

Journal of Cell Science

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Talin binds to β-integrin tails to activate integrins, regulating cell migration, invasion and metastasis. There are two talin genes, TLN1 and TLN2, encoding talin1 and talin2, respectively. Talin1 regulates focal adhesion dynamics, cell migration and invasion, whereas the biological function of talin2 is not clear and, indeed, talin2 has been presumed to function redundantly with talin1. Here, we show that talin2 has a much stronger binding to β-integrin tails than talin1. Replacement of talin2 Ser339 with Cys significantly decreased its binding to β1-integrin tails to a level comparable to that of talin1. Talin2 localizes at invadopodia and is indispensable for the generation of traction force and invadopodium-mediated matrix degradation. Ablation of talin2 suppressed traction force generation and invadopodia formation, which were restored by re-expressing talin2 but not talin1. Furthermore, re-expression of wild-type talin2 (but not talin2 S339C ) in talin2-depleted cells rescued development of traction force and invadopodia. These results suggest that a strong interaction of talin2 with integrins is required to generate traction, which in turn drives invadopodium-mediated matrix degradation, which is key to cancer cell invasion.

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RIAM and Vinculin Binding to Talin Are Mutually Exclusive and Regulate Adhesion Assembly and Turnover

Cited by 189 publications

References 48 publications

The tale of two talins – two isoforms to fine‐tune integrin signalling

The tale of two talins – two isoforms to fine‐tune integrin signalling

Talin – the master of integrin adhesions

Talin2-mediated traction force drives matrix degradation and cell invasion

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