Nano-mechanical characterization of tension-sensitive helix bundles in talin rod

Maki, Kosuke; Nakao, N.; Adachi, Taiji

doi:10.1016/j.bbrc.2017.01.127

Cited by 6 publications

(4 citation statements)

References 38 publications

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“…The most recognized effect of force loading to talin consists in its unfolding to expose cryptic hydrophobic binding sites to host vinculin head ( del Rio et al, 2009 ; Hirata et al, 2014 ; Maki et al, 2017 ; Rahikainen et al, 2017 ). In the absence of force, talin rod remains fully structured, and no vinculin binding sites (VBS) are available; under low-force regimes, only the weakest bundle unfolds revealing its VBS.…”

Section: Focal Adhesions: the Main Hub For Cell-matrix Interactionmentioning

confidence: 99%

Cellular Mechanotransduction: From Tension to Function

et al. 2018

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Living cells are constantly exposed to mechanical stimuli arising from the surrounding extracellular matrix (ECM) or from neighboring cells. The intracellular molecular processes through which such physical cues are transformed into a biological response are collectively dubbed as mechanotransduction and are of fundamental importance to help the cell timely adapt to the continuous dynamic modifications of the microenvironment. Local changes in ECM composition and mechanics are driven by a feed forward interplay between the cell and the matrix itself, with the first depositing ECM proteins that in turn will impact on the surrounding cells. As such, these changes occur regularly during tissue development and are a hallmark of the pathologies of aging. Only lately, though, the importance of mechanical cues in controlling cell function (e.g., proliferation, differentiation, migration) has been acknowledged. Here we provide a critical review of the recent insights into the molecular basis of cellular mechanotransduction, by analyzing how mechanical stimuli get transformed into a given biological response through the activation of a peculiar genetic program. Specifically, by recapitulating the processes involved in the interpretation of ECM remodeling by Focal Adhesions at cell-matrix interphase, we revise the role of cytoskeleton tension as the second messenger of the mechanotransduction process and the action of mechano-responsive shuttling proteins converging on stage and cell-specific transcription factors. Finally, we give few paradigmatic examples highlighting the emerging role of malfunctions in cell mechanosensing apparatus in the onset and progression of pathologies.

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Section: Focal Adhesions: the Main Hub For Cell-matrix Interactionmentioning

confidence: 99%

Cellular Mechanotransduction: From Tension to Function

et al. 2018

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“…Using the new AFM-TIRF system, we directly observed the recruitment of full-length vinculin to the M 1 -M 3 domains of α-catenin under tension. In the context of mechanobiology, certain proteins have been identified as mechano-chemical transducers or mechano-sensors, which expose a cryptic binding site under mechanical force to recruit other proteins 13 , 36 – 39 . However, the identification and characterization of mechano-sensor proteins is still at the development stage because of the lack of suitable experimental approaches to directly detect the interaction between proteins under force.…”

Section: Discussionmentioning

confidence: 99%

Real-time TIRF observation of vinculin recruitment to stretched α-catenin by AFM

Maki

Han

Hirano

et al. 2018

Sci Rep

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Adherens junctions (AJs) adaptively change their intensities in response to intercellular tension; therefore, they integrate tension generated by individual cells to drive multicellular dynamics, such as morphogenetic change in embryos. Under intercellular tension, α-catenin, which is a component protein of AJs, acts as a mechano-chemical transducer to recruit vinculin to promote actin remodeling. Although in vivo and in vitro studies have suggested that α-catenin-mediated mechanotransduction is a dynamic molecular process, which involves a conformational change of α-catenin under tension to expose a cryptic vinculin binding site, there are no suitable experimental methods to directly explore the process. Therefore, in this study, we developed a novel system by combining atomic force microscopy (AFM) and total internal reflection fluorescence (TIRF). In this system, α-catenin molecules (residues 276-634; the mechano-sensitive M 1 -M 3 domain), modified on coverslips, were stretched by AFM and their recruitment of Alexa-labeled full-length vinculin molecules, dissolved in solution, were observed simultaneously, in real time, using TIRF. We applied a physiologically possible range of tensions and extensions to α-catenin and directly observed its vinculin recruitment. Our new system could be used in the fields of mechanobiology and biophysics to explore functions of proteins under tension by coupling biomechanical and biochemical information.Adhesive interaction between neighboring cells contributes to the mechanical maintenance of morphogenetic changes in embryos as well as homeostasis in mature tissues [1][2][3] . The dysfunction of proteins involved in intercellular adhesion thus causes a variety of pathologies [4][5][6] . Cadherin-based adherens junctions (AJs) connect the actin cytoskeleton between cells and dynamically change the strength of adhesion in response to intercellular tension [7][8][9][10][11][12] . During AJ maturation, α-catenin and vinculin cooperate to remodel the actin cytoskeleton [13][14][15] . α-Catenin participates in the cadherin-catenin complex (CCC), whereas cadherin, β-catenin, and α-catenin serially associate together [16][17][18] . The CCC interacts with actin filaments via α-catenin in the cytoplasmic region of AJs to transmit intercellular tension generated by the actomyosin cytoskeleton 19,20 . Under intercellular tension, α-catenin recruits vinculin 13 , which is another key protein in the architecture of AJs. The C-terminus of vinculin interacts with monomeric and filamentous actin to mediate the link between α-catenin and another actin filament 21 . α-Catenin and vinculin thereby induce local remodeling of the actin cytoskeleton at AJs to increase the strength of adhesion 22 , which stably transmits intercellular tension. α-Catenin under tension-free conditions is known to form an autoinhibited conformation against vinculin 23,24 ; the vinculin binding site (VBS, residues 325-360) is embedded in the M 1 domain (residues 273-393) of α-catenin, which is further stabilized by the ...

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“…Then, talin and actin localize into the cell adhesion region to form an integrin-talin-actin complex [12]. Eventually, to bind to vinculin, talin changes its conformation by exposing its cryptic vinculin-binding site [13][14][15][16]. These sequential molecular events lead to a reinforced connection between integrin and the actin filament [16,17].…”

Section: Introductionmentioning

confidence: 99%