Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP

Moreno-Vicente, Roberto; Pavón, Dácil M.; Martín‐Padura, Inés; Català-Montoro, Mauro; Díez-Sánchez, Alberto; Quílez-Álvarez, Antonio; López, Juan Antonio; Sánchez-Álvarez, Miguel; Vázquez, Jesús; Strippoli, Raffaele; Pozo, Miguel Á. del

doi:10.1016/j.celrep.2019.01.090

Cited by 34 publications

(42 citation statements)

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“…Caveolae have been found to contribute to mechanosensing in response to various mechanical stimuli, such as membrane stretching, shear stress, hypoosmotic shock, and cell detachment in various cells. 31,58 It has been proposed that caveolar invitations in the plasma membrane flatten when mechanical tension is imposed upon the membrane, buffering tension forces, and triggering eliciting signals to induce adaptive responses. 20,21 Such a change in membrane curvature could be the trigger to activate piezo1 channels residing within caveolae.…”

Section: Discussionmentioning

confidence: 99%

Mechanical stretch activates piezo1 in caveolae of alveolar type I cells to trigger ATP release and paracrine stimulation of surfactant secretion from alveolar type II cells

et al. 2020

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Secretion of pulmonary surfactant in the alveoli of the lungs is essential to maintain lung function. Stretching of alveoli during lung inflation is the main trigger for surfactant secretion. Yet, the molecular mechanisms how mechanical distension of alveoli results in surfactant secretion are still elusive. The alveolar epithelium consists of alveolar epithelial type I (ATI) and surfactant secreting type II (ATII) cells. ATI, but not ATII cells, express caveolae, small plasma membrane invaginations that can respond to plasma membrane stresses and serve mechanotransductive roles. Within this study, we investigated the role of caveolae as mechanosensors in the alveolus. We generated a human caveolin‐1 knockout ATI cell (hAELVicav−/−) using CRISPR/Cas9. Wildtype (hAELViwt) and hAELVicav−/− cells grown on flexible membranes responded to increasing stretch amplitudes with rises in intracellular Ca2+. The response was less frequent and started at higher stretch amplitudes in hAELVicav−/− cells. Stretch‐induced Ca2+‐signals depended on Ca2+‐entry via piezo1 channels, localized within caveolae in hAELViwt and primary ATI cells. Ca2+‐entry via piezo1 activated pannexin‐1 hemichannels resulting in ATP release from ATI cells. ATP release was reduced in hAELVicav−/− cells. In co‐cultures resembling the alveolar epithelium, released ATP stimulated Ca2+ signals and surfactant secretion from neighboring ATII cells when co‐cultured with hAELViwt but not hAELVicav−/− cells. In summary, we propose that caveolae in ATI cells are mechanosensors within alveoli regulating stretch‐induced surfactant secretion from ATII cells.

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Section: Discussionmentioning

confidence: 99%

Mechanical stretch activates piezo1 in caveolae of alveolar type I cells to trigger ATP release and paracrine stimulation of surfactant secretion from alveolar type II cells

et al. 2020

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“…This mechanical control depends on RHO GTPase function and actomyosin-driven contractility but is largely independent of kinase regulation. 32 The state of the actin cytoskeleton plays a key role in mediating the effects of shape and tension of nuclear YAP/TAZ. Disturbances of the actin cytoskeleton have strong effects on YAP localization.…”

Section: Discussionmentioning

confidence: 99%

“…Note that the Hippo, Hedgehog, mTOR, and Wnt signaling pathways are all significantly downregulated after Chsy3 knockout. G, The Gene Set Enrichment Analysis (GSEA) showed that only Hippo pathway is significantly affected comparing Chsy3 −/− and WT NP cell data actin assembly, 32 we thus hypothesized that extracellular CS mediated actin assembly of the NP cells may be responsible for the activation of Yap1 in NP cells. To test this, we used Latrunculin A (Lat.A, 100 nM) to inhibit actin assembly in NP cells and found more severe degeneration phenotype ( Figure 7E).…”

Section: Actin Tension Is Involved In Chsy3 Mediated Yap1 Activationmentioning

confidence: 95%

Chondroitin synthase‐3 regulates nucleus pulposus degeneration through actin‐induced YAP signaling

Wei

Cao

et al. 2020

FASEB j.

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“…This mechanism has not been demonstrated in the context of ECM elasticity. However, caveolae play a role in sustaining actomyosin contractility, ECM remodeling and the responses to ECM stiffness [38,39].…”

Section: Downstream Pathways Modulated By Forcesmentioning

confidence: 99%

Mechanical Forces as Determinants of Disseminated Metastatic Cell Fate

Montagner

Dupont

2020

Cells

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Disseminated metastatic cancer cells represent one of the most relevant causes of disease relapse and associated death for cancer patients, and a therapeutic target of the highest priority. Still, our understanding of how disseminated cancer cells survive in the foreign metastatic environment, and eventually cause metastatic outgrowth, remains rather limited. In this review we focus on the cell microenvironment as a key regulator of cell behavior at the metastatic site, and especially on the mechanical properties of the extracellular matrix and associated integrin signaling. We discuss available evidence pointing to a pervasive role of extracellular matrix (ECM) mechanical properties in regulating cancer cell proliferation and survival after dissemination, and propose that this might represent an important bottleneck for cells invading and establishing into a novel tissue. We point to the known molecular players, how these might contribute to modulate the mechanical properties of the metastatic environment, and the response of cells to these cues. Finally, we propose that emerging knowledge on the physical interaction of disseminated metastatic cells and on the downstream mechanotransduction pathways, including YAP/TAZ (Yes-associated protein-1 and WW-domain transcription activator 1) and MRTFs (Myocardin-related transcription factors), may help to identify novel approaches for therapy.

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Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP

Cited by 34 publications

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Mechanical stretch activates piezo1 in caveolae of alveolar type I cells to trigger ATP release and paracrine stimulation of surfactant secretion from alveolar type II cells

Mechanical stretch activates piezo1 in caveolae of alveolar type I cells to trigger ATP release and paracrine stimulation of surfactant secretion from alveolar type II cells

Chondroitin synthase‐3 regulates nucleus pulposus degeneration through actin‐induced YAP signaling

Mechanical Forces as Determinants of Disseminated Metastatic Cell Fate

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