Mechanosensation: A Catch Bond That Only Hooks One Way

Swaminathan, Vinay; Alushin, Gregory M.; Waterman, Clare M.

doi:10.1016/j.cub.2017.09.023

Cited by 12 publications

(13 citation statements)

References 21 publications

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“…In their parallel work, Xu et al speculate that the displacement of H1 from the α-catenin ABD upon actin binding could be stabilized or induced by force ( Xu et al, 2020 ), providing a possible structural mechanism for catch-bond formation which we have previously proposed could also be employed by vinculin ( Kim et al, 2016 ; Swaminathan et al, 2017 ). This model predicts that the force required to dissociate H1 from the α-catenin ABD should be lower than the force required to displace the ABD in the mechanically-reinforced, strongly bound state from F-actin.…”

Section: Discussionmentioning

confidence: 91%

Molecular mechanism for direct actin force-sensing by α-catenin

Mei

Reyes

Reynolds

et al. 2020

eLife

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The actin cytoskeleton mediates mechanical coupling between cells and their tissue microenvironments. The architecture and composition of actin networks are modulated by force, but it is unclear how interactions between actin filaments (F-actin) and associated proteins are mechanically regulated. Here, we employ both optical trapping and biochemical reconstitution with myosin motor proteins to show single piconewton forces applied solely to F-actin enhance binding by the human version of the essential cell-cell adhesion protein αE-catenin, but not its homolog vinculin. Cryo-electron microscopy structures of both proteins bound to F-actin reveal unique rearrangements that facilitate their flexible C-termini refolding to engage distinct interfaces. Truncating α-catenin's C-terminus eliminates force-activated F-actin binding, and addition of this motif to vinculin confers force-activated binding, demonstrating that α-catenin's C-terminus is a modular detector of F-actin tension. Our studies establish that piconewton force on F-actin can enhance partner binding, which we propose mechanically regulates cellular adhesion through a-catenin.

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Section: Discussionmentioning

confidence: 91%

Molecular mechanism for direct actin force-sensing by α-catenin

Mei

Reyes

Reynolds

et al. 2020

eLife

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“…The ability of cells to sense not only the magnitude of a physical stimulus, but also its direction, has been observed in different contexts and appears to involve integrins (Swaminathan et al, 2017a). Even though the molecular mechanism underlying the ability to sense the direction of mechanical cues remains rather obscure, recent data show that the interaction of vinculin and actin downstream of integrins occurs by forming a force-dependent catch bond that strongly depends on the direction of the applied force, and computational modeling suggests that the vinculin-actin catch bond might represent a mechanism for cellular responses to directional forces (Huang et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation

Albarrán-Juárez

Iring

Wang

et al. 2018

Journal of Experimental Medicine

209

211

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The vascular endothelium is constantly exposed to mechanical forces, including fluid shear stress exerted by the flowing blood. Endothelial cells can sense different flow patterns and convert the mechanical signal of laminar flow into atheroprotective signals, including eNOS activation, whereas disturbed flow in atheroprone areas induces inflammatory signaling, including NF-κB activation. How endothelial cells distinguish different flow patterns is poorly understood. Here we show that both laminar and disturbed flow activate the same initial pathway involving the mechanosensitive cation channel Piezo1, the purinergic P2Y receptor, and G/G-mediated signaling. However, only disturbed flow leads to Piezo1- and G/G-mediated integrin activation resulting in focal adhesion kinase-dependent NF-κB activation. Mice with induced endothelium-specific deficiency of Piezo1 or Gα/Gα show reduced integrin activation, inflammatory signaling, and progression of atherosclerosis in atheroprone areas. Our data identify critical steps in endothelial mechanotransduction, which distinguish flow pattern-dependent activation of atheroprotective and atherogenic endothelial signaling and suggest novel therapeutic strategies to treat inflammatory vascular disorders such as atherosclerosis.

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“…We have found interesting structural transitions in actin during the mechanochemical cycle of myosin VI and conformational changes in the motor, that could be regulated by force to control nucleotide release (2). We have also observed an interesting unfolding transition of the actin-binding domain of the adhesion protein vinculin when it binds actin (3), which could be reinforced by tension and explains the ability of vinculin to form directional catch-bonds with the actin filament (4). However, in both of these studies we solved structures in the absence of force and then inferred how force could impact the structures we observed.…”

Section: What Are You Currently Working On and What Is Up Next For You?mentioning

confidence: 96%