Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity

Kumar, Abhishek; Ouyang, Mingxing; Dries, Koen van den; McGhee, Ewan J.; Tanaka, Keiichiro; Anderson, Marie; Groisman, Alexander; Goult, Benjamin T.; Anderson, Kurt I.; Schwartz, Martin A.

doi:10.1083/jcb.201510012

Cited by 232 publications

(274 citation statements)

References 62 publications

(75 reference statements)

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“…myosin II-dependent (Austen et al, 2015;Kumar et al, 2016). In contrast, the amount of force on vinculin does not change with substrate stiffness (Kumar et al, 2016), consistent with it being a mechanoeffector rather than a mechanosensor.…”

Section: Box 2 Testing the Importance Of Inside-out Integrin Activatmentioning

confidence: 71%

“…In contrast, the amount of force on vinculin does not change with substrate stiffness (Kumar et al, 2016), consistent with it being a mechanoeffector rather than a mechanosensor. Deletion or mutation of ABS3 causes only a slight reduction in the force sensed across talin (Austen et al, 2015;Kumar et al, 2016), but blocks the normal reduction of force on talin in central fibrillar adhesions versus peripheral focal adhesions through an unknown mechanism (Kumar et al, 2016). In contrast, mutating ABS2 or deleting both ABS2 and ABS3 substantially reduces force across talin and eliminates its ability to recruit vinculin.…”

Section: Box 2 Testing the Importance Of Inside-out Integrin Activatmentioning

confidence: 79%

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Talin – the master of integrin adhesions

Klapholz

Brown

2017

Journal of Cell Science

264

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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Section: Box 2 Testing the Importance Of Inside-out Integrin Activatmentioning

confidence: 71%

Section: Box 2 Testing the Importance Of Inside-out Integrin Activatmentioning

confidence: 79%

Talin – the master of integrin adhesions

Klapholz

Brown

2017

Journal of Cell Science

264

222

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“…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. As domains unfold, the binding sites for ligands that engage the folded rod domains are destroyed, as is the case for RIAM binding to R3.…”

Section: Talin1 and Talin2 Rod Interactionsmentioning

confidence: 99%

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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“…Increasing ECM stiffness leads to elevated Rho activity (Paszek et al, 2005); therefore, it is possible that this, in turn, through a downstream increase of actomyosin tension, leads to increased activation of talin and vinculin in adhesion sites. Indeed, it has been shown by using a talin tension sensor construct, that the amount of tension across talin is modified by substrate stiffness and that vinculin is required for the maximal tension to be applied through talin at FAs (Austen et al, 2015;Kumar et al, 2016).…”

Section: The Relationship Between Protein Dynamics and Mechanosensingmentioning

confidence: 99%

Distinct focal adhesion protein modules control different aspects of mechanotransduction

Stutchbury

Atherton

Tsang

et al. 2017

Journal of Cell Science

169

142

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Focal adhesions (FAs) are macromolecular complexes that regulate cell adhesion and mechanotransduction. By performing fluorescence recovery after photobleaching (FRAP) and fluorescence loss after photoactivation (FLAP) experiments, we found that the mobility of core FA proteins correlates with their function. Structural proteins such as tensin, talin and vinculin are significantly less mobile in FAs than signaling proteins such as FAK (also known as PTK2) and paxillin. The mobilities of the structural proteins are directly influenced by substrate stiffness, suggesting that they are involved in sensing the rigidity of the extracellular environment. The turnover rates of FAK and paxillin, as well as kindlin2 (also known as FERMT2), are not influenced by substrate stiffness. By using specific Src and FAK inhibitors, we reveal that force-sensing by vinculin occurs independently of FAK and paxillin phosphorylation. However, their phosphorylation is required for downstream Rac1-driven cellular processes, such as protrusion and cell migration. Overall, we show that the FA is composed of different functional modules that separately control mechanosensing and the cellular mechano-response.

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Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity

Cited by 232 publications

References 62 publications

Talin – the master of integrin adhesions

Talin – the master of integrin adhesions

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

Distinct focal adhesion protein modules control different aspects of mechanotransduction

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