αvβ3 integrins negatively regulate cellular forces by phosphorylation of its distal NPXY site

Milloud, Rachel; Destaing, Olivier; Mets, Richard De; Bourrin-Reynard, Ingrid; Oddou, Christiane; Delon, Antoine; Wang, Irène; Albigès-Rizo, Corinne; Balland, Martial

doi:10.1111/boc.201600041

Cited by 27 publications

(28 citation statements)

References 46 publications

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“…In this regard, specific combinations of α-β integrins are known to play different roles in mechanosensing and force generation ( Seetharaman and Etienne-Manneville, 2018 ). Although the mechanical responsiveness of the integrins appears to be diverse, single cell tensional homeostasis is finely tuned mainly by an equilibrium between β3 and β1 integrins ( Milloud et al, 2017 ). In fact, deletion of β3 causes traction forces to increase, whereas the deletion of β1 integrin results in a strong decrease of contractile forces.…”

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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“…However, the loss of α 5 β 1 can be compensated by α V β 3 to regulate force transmission [Balcioglu et al., ]. Although β 1 and β 3 bind to the same ligand, they have distinct but cooperative roles in force transmission in mouse embryonic fibroblasts [Milloud et al., ]. In contrast, adhesions through α 6 β 1 or α L β 2 in CHO.B2 cells are not altered by myosin II and exert reduced forces on the substrate in comparison with α 5 β 1 , suggesting that the intracellular forces are not transmitted effectively to the substratum due to alterations in the molecular clutch [Chen et al., ].…”

Section: Textmentioning

confidence: 99%

Integrin diversity brings specificity in mechanotransduction

Seetharaman

Etienne-Manneville

2018

Biology of the Cell

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Cells sense and respond to the biochemical and physical properties of the extracellular matrix (ECM) through adhesive structures that bridge the cell cytoskeleton and the surrounding environment. Integrin-mediated adhesions interact with specific ECM proteins and sense the rigidity of the substrate to trigger signalling pathways that, in turn, regulate cellular processes such as adhesion, motility, proliferation and differentiation. This process, called mechanotransduction, influenced by the involvement of different integrin subtypes and their high ECM-ligand binding specificity, contributes to the cell-type-specific mechanical responses. In this review, we describe how the expression of particular integrin subtypes affects cellular adaptation to substrate rigidity. We then explain the role of integrins and associated proteins in mechanotransduction, focusing on their specificity in mechanosensing and force transmission.

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“…For all of these readouts, averaged values of several individual cells are typically used to represent cell traction forces. However, the wide range of forces, which has a non-Gaussian asymmetric distribution starting at very low values and ending with a long tail (e.g., Figure 1 in Milloud et al. , 2017) tends to be overlooked but is manifest when all individual values are reported.…”

Section: Variability In Traction Force Measurementsmentioning

confidence: 99%

Dissipation of contractile forces: the missing piece in cell mechanics

Kurzawa

Vianay

Senger

et al. 2017

MBoC

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Mechanical forces are key regulators of cell and tissue physiology. The basic molecular mechanism of fiber contraction by the sliding of actin filament upon myosin leading to conformational change has been known for decades. The regulation of force generation at the level of the cell, however, is still far from elucidated. Indeed, the magnitude of cell traction forces on the underlying extracellular matrix in culture is almost impossible to predict or experimentally control. The considerable variability in measurements of cell-traction forces indicates that they may not be the optimal readout to properly characterize cell contractile state and that a significant part of the contractile energy is not transferred to cell anchorage but instead is involved in actin network dynamics. Here we discuss the experimental, numerical, and biological parameters that may be responsible for the variability in traction force production. We argue that limiting these sources of variability and investigating the dissipation of mechanical work that occurs with structural rearrangements and the disengagement of force transmission is key for further understanding of cell mechanics.

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αvβ3 integrins negatively regulate cellular forces by phosphorylation of its distal NPXY site

Cited by 27 publications

References 46 publications

Cellular Mechanotransduction: From Tension to Function

Cellular Mechanotransduction: From Tension to Function

Integrin diversity brings specificity in mechanotransduction

Dissipation of contractile forces: the missing piece in cell mechanics

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