Vinculin Is a Dually Regulated Actin Filament Barbed End-capping and Side-binding Protein

Clainche, Christophe Le; Dwivedi, Satya Prakash; Didry, Dominique; Carlier, Marie-France

doi:10.1074/jbc.m110.102830

Cited by 72 publications

(99 citation statements)

References 55 publications

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“…In cells, multiple parameters can modify the activity of proteins, such as the charge of membrane lipids, the addition of phosphate groups by kinases, local gradients of pH and cations, crowding effects or the binding of partners. Hence, in many instances, it proved informative to screen a variety of physico-chemical conditions, including a mild reduction in ionic strength, before establishing the activity of actin-binding proteins such as formins, VASP or vinculin (5,31,32). Here, varying the ionic strength was sufficient to reveal a new inhibitory activity of ABD1 ( Figure 1A).…”

Section: Resultsmentioning

confidence: 98%

“…Talin ABD1 inhibits actin filament barbed end elongation − To determine the ability of talin constructs to regulate actin assembly ( Figure S1A, C), we first monitored barbed end elongation by measuring the increase in pyrenyl-labeled actin fluorescence upon polymerization in the presence of spectrin-actin seeds (5). In cells, multiple parameters can modify the activity of proteins, such as the charge of membrane lipids, the addition of phosphate groups by kinases, local gradients of pH and cations, crowding effects or the binding of partners.…”

Section: Resultsmentioning

confidence: 99%

“…Talin adds up to the list of proteins that target actin filaments barbed ends in FAs, including VASP, vinculin, tensin and formins (5,7,8,36). Like vinculin tail, talin ABD1 binds to the side of actin filaments and inhibits barbed-end elongation.…”

Section: Discussionmentioning

confidence: 99%

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Integrin-bound talin head inhibits actin filament barbed-end elongation

Ciobănaşu¹,

Wang²,

Henriot³

et al. 2018

Journal of Biological Chemistry

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Focal adhesions (FAs) mechanically couple the extracellular matrix (ECM) to the dynamic actin cytoskeleton, via transmembrane integrins and actin-binding proteins. The molecular mechanisms by which protein machineries control force transmission along this molecular axis, i.e. modulating integrin activation and controlling actin polymerization, remain largely unknown. Talin is a major actin-binding protein that controls both the inside-out activation of integrins and actin-filament anchoring and thus plays a major role in the establishment of the actin-ECM mechanical coupling. Talin contains three actinbinding domains (ABDs). The N-terminal head domain contains both the F3 integrin-activating domain and ABD1, while the C-terminal rod contains the actin-anchoring ABD2 and ABD3. Integrin binding is regulated by an intramolecular interaction between the N-terminal head and a Cterminal five-helix-bundle (R9). Whether talin ABDs regulate actin polymerization in a constitutive or regulated manner has not been fully explored. Here, we combine kinetics assays using fluorescence spectroscopy and single actin filament observation in TIRF microscopy, to examine relevant functions of the three ABDs of talin. We find that the N-terminal ABD1 blocks actin filament barbed end elongation while ABD2 and ABD3 do not show any activity. By mutating residues in ABD1, we find that this activity is mediated by a positively charged surface that is partially masked by its intramolecular interaction with R9. Our results also demonstrate that, once this intramolecular interaction is released, integrinbound talin head retains the ability to inhibit actin assembly.Cell adhesion to the extracellular matrix plays a critical role in many physiological functions such as cell migration, invasion or epithelial basement membrane attachment. Among the multiple adhesion structures, focal adhesions (FAs) play a major role (1,2). These multiprotein complexes couple various extracellular matrices to the actin cytoskeleton via the transmembrane heterodimeric αβ integrins and actin-binding proteins (ABPs) (3,4). The control of actin polymerization by ABPs is thought to play an important role to initiate the formation of the actomyosin stress fibers and control their tension by modulating their elongation. We showed previously that vinculin blocks actin filament barbed end elongation (5), while others reported that VASP promotes the elongation of actin filament barbed ends in a processive-like manner (6,7). Several formins may also play a role in the formation and elongation of Talin head inhibits actin assembly 2 stress fibers (8). However, despite these isolated characterizations, the respective roles of the multiple ABPs and their coordination in this process are poorly understood. The actin-binding protein talin plays a major role in FAs (9) ( Figure S1). First it acts very early to activate integrins. In this process the N-terminal PTB (phosphotyrosine binding) domain, located in the head domain of talin, also known as the F3 subdomain of the ...

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Integrin-bound talin head inhibits actin filament barbed-end elongation

Ciobănaşu¹,

Wang²,

Henriot³

et al. 2018

Journal of Biological Chemistry

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“…Furthermore, Aragona et al showed that knockdown of the F-actin capping or severing proteins CapZ, cofilin and gelsolin, increases F-actin bundling and promotes the nuclear localization of YAP/TAZ on soft ECM (Aragona et al, 2013). Interestingly, vinculin directly binds to Factin (Jockusch and Isenberg, 1981;Menkel et al, 1994) and has F-actin-bundling and -capping activities (Le Clainche et al, 2010;Wen et al, 2009). Here, we demonstrated that actin-bindingdeficient vinculin I997A (Thompson et al, 2014) lacks the ability to promote the change in the YAP/TAZ nuclear localization that is dependent on ECM stiffness.…”

Section: Discussionmentioning

confidence: 99%

Vinculin promotes nuclear localization of TAZ to inhibit ECM stiffness-dependent differentiation into adipocytes

Kuroda

Wada

Kimura

et al. 2017

Journal of Cell Science

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Extracellular matrix (ECM) stiffness regulates the lineage commitment of mesenchymal stem cells (MSCs). Although cells sense ECM stiffness through focal adhesions, how cells sense ECM stiffness and regulate ECM stiffness-dependent differentiation remains largely unclear. In this study, we show that the cytoskeletal focal adhesion protein vinculin plays a critical role in the ECM stiffness-dependent adipocyte differentiation of MSCs. ST2 mouse MSCs differentiate into adipocytes and osteoblasts in an ECM stiffness-dependent manner. We find that a rigid ECM increases the amount of cytoskeleton-associated vinculin and promotes the nuclear localization and activity of the transcriptional coactivator paralogs Yes-associated protein (YAP, also known as YAP1) and transcriptional coactivator with a PDZ-binding motif (TAZ, also known as WWTR1) (hereafter YAP/TAZ). Vinculin is necessary for enhanced nuclear localization and activity of YAP/TAZ on the rigid ECM but it does not affect the phosphorylation of the YAP/TAZ kinase LATS1. Furthermore, vinculin depletion promotes differentiation into adipocytes on rigid ECM, while it inhibits differentiation into osteoblasts. Finally, TAZ knockdown was less effective at promoting adipocyte differentiation in vinculin-depleted cells than in control cells. These results suggest that vinculin promotes the nuclear localization of transcription factor TAZ to inhibit the adipocyte differentiation on rigid ECM.

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“…In addition to increasing the binding of F-actin, vinculin might bring other factors to cadherin adhesions, such as members of the vasodilator-stimulated phosphoprotein (VASP) (Brindle et al, 1996) and ponsin families (Kioka et al, 1999;Mandai et al, 1999), as well as the ARP2/3 complex (DeMali et al, 2002;Tang and Brieher, 2012), to regulate Factin remodeling. Moreover, there is evidence that vinculin itself has an actin-polymerization activity in its tail domain (Le Clainche et al, 2010;Wen et al, 2009). Therefore, a forcedependent increase in actin polymerization at cell-cell junctions might serve to counteract the pulling force that is exerted by contractile F-actin.…”

Section: A-catenin and Vinculin -A Central Protein Pair In Cadherin Mmentioning

confidence: 99%

Mechanosensitive systems at the cadherin–F-actin interface

Huveneers

Rooij

2013

Journal of Cell Science

201

189

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SummaryCells integrate biochemical and mechanical information to function within multicellular tissue. Within developing and remodeling tissues, mechanical forces contain instructive information that governs important cellular processes that include stem cell maintenance, differentiation and growth. Although the principles of signal transduction (protein phosphorylation, allosteric regulation of enzymatic activity and binding sites) are the same for biochemical and mechanical-induced signaling, the first step of mechanosensing, in which protein complexes under tension transduce changes in physical force into cellular signaling, is very different, and the molecular mechanisms are only beginning to be elucidated. In this Commentary, we focus on mechanotransduction at cell-cell junctions, aiming to comprehend the molecular mechanisms involved. We describe how different junction structures are associated with the actomyosin cytoskeleton and how this relates to the magnitude and direction of forces at cell-cell junctions. We discuss which cell-cell adhesion receptors have been shown to take part in mechanotransduction. Then we outline the force-induced molecular events that might occur within a key mechanosensitive system at cell-cell junctions; the cadherin-F-actin interface, at which a-catenin and vinculin form a central module. Mechanotransduction at cell-cell junctions emerges as an important signaling mechanism, and we present examples of its potential relevance for tissue development and disease.

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Vinculin Is a Dually Regulated Actin Filament Barbed End-capping and Side-binding Protein

Cited by 72 publications

References 55 publications

Integrin-bound talin head inhibits actin filament barbed-end elongation

Integrin-bound talin head inhibits actin filament barbed-end elongation

Vinculin promotes nuclear localization of TAZ to inhibit ECM stiffness-dependent differentiation into adipocytes

Mechanosensitive systems at the cadherin–F-actin interface

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