Talin as a mechanosensitive signaling hub

Goult, Benjamin T.; Yan, Jie; Schwartz, Martin A.

doi:10.1083/jcb.201808061

Cited by 195 publications

(250 citation statements)

References 93 publications

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“…[25][26][27] In support of these findings, FA proteins have been shown to be intrinsically mechanosensitive. Examples of this can be observed in the member of the mechanosensitive Cas family, p130Cas, which was shown to become extended and phosphorylated under tension, 28 zyxin which is recruited to strained areas along actin fibers, thereby regulating their elasticity, 29 talin, which was demonstrated to alter conformation as a function of force exertion, 30,31 and vinculin, which requires force to localize to FA compelxes. 25,27 Quantitative measurements using cytoskeleton laser nanosurgery also provided evidence of direct actin stress fiber association to the substrate, recruiting FA proteins such as zyxin to areas with highest tensed anchorage.…”

Section: The Cytoskeleton and Mechanosensitive Moleculesmentioning

confidence: 99%

Lymphocyte mechanotransduction: The regulatory role of cytoskeletal dynamics in signaling cascades and effector functions

Ben‐Shmuel¹,

Joseph²,

Sabag³

et al. 2019

Journal of Leukocyte Biology

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The process of mechanotransduction, that is, conversion of physical forces into biochemical signaling cascades, has attracted interest as a potential mechanism for regulating immune cell activation. The cytoskeleton serves a critical role in a variety of lymphocyte functions, from cellular activation, proliferation, adhesion, and migration, to creation of stable immune synapses, and execution of functions such as directed cytotoxicity. Though traditionally considered a scaffold that enables formation of signaling complexes that maintain stable immune synapses, the cytoskeleton was additionally shown to play a dynamic role in lymphocyte signaling cascades by sensing physical cues such as substrate rigidity, and transducing these mechanical features into chemical signals that ultimately influence lymphocyte effector functions. It is thus becoming clear that cytoskeletal dynamics are essential for the lymphocyte response, beyond the role of the cytoskeleton as a stationary framework. Here, we describe the transduction of extracellular forces to activate signaling pathways and effector functions mediated through the cytoskeleton in lymphocytes. We also highlight recent discoveries of cytoskeleton‐mediated mechanotransduction on intracellular signaling pathways in NK cells.

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Section: The Cytoskeleton and Mechanosensitive Moleculesmentioning

confidence: 99%

Lymphocyte mechanotransduction: The regulatory role of cytoskeletal dynamics in signaling cascades and effector functions

Ben‐Shmuel¹,

Joseph²,

Sabag³

et al. 2019

Journal of Leukocyte Biology

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“…Talin1 and 2 are cytoplasmic adapters that provide a direct mechanosensitive link between the integrin family of cell adhesion molecules and the actin cytoskeleton (Calderwood et al, 2013;Goult et al, 2018). Talins are comprised of an N-terminal atypical FERM domain (Elliott et al, 2010), coupled via a flexible linker to a large rod domain comprised of 63 helices arranged into 13 helical bundles, R1-R13 ( Fig.1A) (Goult et al, 2013;Gough and Goult, 2018).…”

Section: Introductionmentioning

confidence: 99%

Talin Rod Domain Containing Protein 1 (TLNRD1) is a novel actin-bundling protein which promotes filopodia formation

Cowell

Jacquemet

Singh

et al. 2020

Preprint

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Talin is a mechanosensitive adapter protein which couples integrins to the cytoskeleton and regulates integrin-mediated adhesion. Talin rod domain-containing protein-1 (TLNRD1) shares 22% homology with the R7R8 domains of talin, and is highly conserved throughout vertebrate evolution, however little is known about its function. Here we show that TLNRD1 is an α-helical protein which shares the same atypical topology as talin R7R8, but forms a novel antiparallel dimer arrangement. Actin co-sedimentation assays and electron microscopy reveal TLNRD1 is an actin-bundling protein that forms tight actin bundles. In addition, TLNRD1 binds to the same LD-motif containing proteins, RIAM and KANK, as talin, and thus may act in competition with talin. Filopodia are cell protrusions supported by tightly bundled actin filaments and TLNRD1 localises to filopodia tips, increases filopodia number and promotes cell migration in 2D. Together our results suggest that TLNRD1 has similar functionality to talin R7R8, serving as a nexus between the actin and microtubule cytoskeletons independent of adhesion complexes.

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“…Vinculin is essential for cellular mechanical force sensing . Integrin signaling through talin, paxillin, and vinculin recruits additional actin‐binding proteins to promote cell adhesion and migration . Additionally, integrin‐mediated adhesion sites incorporate the actin‐based motor protein myosin.…”

Section: Introductionmentioning

confidence: 99%

Cells under stress: The mechanical environment shapes inflammasome responses to danger signals

Joshi

Morley

2019

Journal of Leukocyte Biology

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Many intracellular signals, such as host danger-associated molecules and bacterial toxins during infection, elicit inflammasome activation. However, the mechanical environment in tissues may also influence the sensitivity of various inflammasomes to activation. The cellular mechanical environment is determined by the extracellular tissue stiffness, or its inverse, tissue compliance. Tissue stiffness is sensed by the intracellular cytoskeleton through a process termed mechanotransduction. Thus, extracellular compliance and the intracellular cytoskeleton may regulate the sensitivity of inflammasome activation. Control of proinflammatory signaling by tissue compliance may contribute to the pathogenesis of diseases such as ventilator-induced lung injury during bacterial pneumonia and tissue fibrosis in inflammatory disorders. The responsible signaling cascades in inflammasome activation pathways and mechanotransduction crosstalk are not yet fully understood. This rather different immunomodulatory perspective will be reviewed and open questions discussed here. K E Y W O R D S cell adhesion, inflammasome, inflammation, integrins, mechanobiology, monocytes/macrophages

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Talin as a mechanosensitive signaling hub

Cited by 195 publications

References 93 publications

Lymphocyte mechanotransduction: The regulatory role of cytoskeletal dynamics in signaling cascades and effector functions

Lymphocyte mechanotransduction: The regulatory role of cytoskeletal dynamics in signaling cascades and effector functions

Talin Rod Domain Containing Protein 1 (TLNRD1) is a novel actin-bundling protein which promotes filopodia formation

Cells under stress: The mechanical environment shapes inflammasome responses to danger signals

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