Spatial association of the Cav1.2 calcium channel with α<sub>5</sub>β<sub>1</sub>-integrin

Chao, Jun-Tzu; Gui, Peichun; Zamponi, Gerald W.; Davis, George E.; Davis, Michael J.

doi:10.1152/ajpcell.00171.2010

Cited by 31 publications

(29 citation statements)

References 42 publications

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“…Integrins and the extracellular matrix have been implicated in mechanotransduction in endothelial cells [67], vascular smooth muscle cells [68] and neurons [69]. Mechanical stretch of capillary endothelial cells has been demonstrated to activate TRPV4 channels through an integrin signalling pathway [70].…”

Section: Discussionmentioning

confidence: 99%

Shear stress mediates exocytosis of functional TRPV4 channels in endothelial cells

Baratchi

Almazi

Darby

et al. 2015

Cell. Mol. Life Sci.

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Mechanosensitive ion channels are implicated in the biology of touch, pain, hearing and vascular reactivity; however, the identity of these ion channels and the molecular basis of their activation is poorly understood. We previously found that transient receptor potential vanilloid 4 (TRPV4) is a receptor operated ion channel that is sensitised and activated by mechanical stress. Here, we investigated the effects of mechanical stimulation on TRPV4 localisation and activation in native and recombinant TRPV4-expressing cells. We used a combination of total internal reflection fluorescence microscopy, cell surface biotinylation assay and Ca(2+) imaging with laser scanning confocal microscope to show that TRPV4 is expressed in primary vascular endothelial cells and that shear stress sensitises the response of TRPV4 to its agonist, GSK1016790A. The sensitisation was attributed to the recruitment of intracellular pools of TRPV4 to the plasma membrane, through the clathrin and dynamin-mediated exocytosis. The translocation was dependent on ILK/Akt signalling pathway, release of Ca(2+) from intracellular stores and we demonstrated that shear stress stimulated phosphorylation of TRPV4 at tyrosine Y110. Our findings implicate calcium-sensitive TRPV4 translocation in the regulation of endothelial responses to mechanical stimulation.

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Section: Discussionmentioning

confidence: 99%

Shear stress mediates exocytosis of functional TRPV4 channels in endothelial cells

Baratchi

Almazi

Darby

et al. 2015

Cell. Mol. Life Sci.

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“…The importance of integrins in regulating the activity of ion channels has been demonstrated in several cell types, including vascular smooth muscle (49,50), endothelium, (51) and neurons (52). In the myocardium, integrin activation is necessary for mechano-electrical transduction, as evidenced by the fact that the increased beating rate caused by shear stress in ventricular myocytes can be prevented by integrin inhibition (27).…”

Section: Discussionmentioning

confidence: 99%

Shear stress triggers insertion of voltage-gated potassium channels from intracellular compartments in atrial myocytes

Boycott

Barbier

Eichel

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Atrial myocytes are continuously exposed to mechanical forces including shear stress. However, in atrial myocytes, the effects of shear stress are poorly understood, particularly with respect to its effect on ion channel function. Here, we report that shear stress activated a large outward current from rat atrial myocytes, with a parallel decrease in action potential duration. The main ion channel underlying the increase in current was found to be Kv1.5, the recruitment of which could be directly observed by total internal reflection fluorescence microscopy, in response to shear stress. The effect was primarily attributable to recruitment of intracellular pools of Kv1.5 to the sarcolemma, as the response was prevented by the SNARE protein inhibitor N-ethylmaleimide and the calcium chelator BAPTA. The process required integrin signaling through focal adhesion kinase and relied on an intact microtubule system. Furthermore, in a rat model of chronic hemodynamic overload, myocytes showed an increase in basal current despite a decrease in Kv1.5 protein expression, with a reduced response to shear stress. Additionally, integrin beta1d expression and focal adhesion kinase activation were increased in this model. This data suggests that, under conditions of chronically increased mechanical stress, the integrin signaling pathway is overactivated, leading to increased functional Kv1.5 at the membrane and reducing the capacity of cells to further respond to mechanical challenge. Thus, pools of Kv1.5 may comprise an inducible reservoir that can facilitate the repolarization of the atrium under conditions of excessive mechanical stress.trafficking | cardiomyocytes | potassium current

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“…For instance, increases in membrane tension that result from actin polymerization can activate contractility and exocytosis , or regulate the activity of stretch-sensitive ion channels (Sbrana et al, 2008). Mechanosensitive ion channels also associate with b1 integrins (Chao et al, 2011), and might be activated by forces transmitted through them (Matthews et al, 2010). Force activation of these channels leads to adhesion reinforcement, and affects migration, contractility and recruitment of vinculin (Matthews et al, 2006;Munevar et al, 2004).…”

Section: Alternative Pathwaysmentioning

confidence: 99%

Finding the weakest link – exploring integrin-mediated mechanical molecular pathways

Roca‐Cusachs

Iskratsch

Sheetz

2012

Journal of Cell Science

227

222

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SummaryFrom the extracellular matrix to the cytoskeleton, a network of molecular links connects cells to their environment. Molecules in this network transmit and detect mechanical forces, which subsequently determine cell behavior and fate. Here, we reconstruct the mechanical pathway followed by these forces. From matrix proteins to actin through integrins and adaptor proteins, we review how forces affect the lifetime of bonds and stretch or alter the conformation of proteins, and how these mechanical changes are converted into biochemical signals in mechanotransduction events. We evaluate which of the proteins in the network can participate in mechanotransduction and which are simply responsible for transmitting forces in a dynamic network. Besides their individual properties, we also analyze how the mechanical responses of a protein are determined by their serial connections from the matrix to actin, their parallel connections in integrin clusters and by the rate at which force is applied to them. All these define mechanical molecular pathways in cells, which are emerging as key regulators of cell function alongside better studied biochemical pathways.

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Spatial association of the Cav1.2 calcium channel with α₅β₁-integrin

Cited by 31 publications

References 42 publications

Shear stress mediates exocytosis of functional TRPV4 channels in endothelial cells

Shear stress mediates exocytosis of functional TRPV4 channels in endothelial cells

Shear stress triggers insertion of voltage-gated potassium channels from intracellular compartments in atrial myocytes

Finding the weakest link – exploring integrin-mediated mechanical molecular pathways

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Spatial association of the Cav1.2 calcium channel with α5β1-integrin

Cited by 31 publications

References 42 publications

Shear stress mediates exocytosis of functional TRPV4 channels in endothelial cells

Shear stress mediates exocytosis of functional TRPV4 channels in endothelial cells

Shear stress triggers insertion of voltage-gated potassium channels from intracellular compartments in atrial myocytes

Finding the weakest link – exploring integrin-mediated mechanical molecular pathways

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Spatial association of the Cav1.2 calcium channel with α₅β₁-integrin