scholarly journals Distinct contributions of tensile and shear stress on E-cadherin levels during morphogenesis

2018 ◽  
Author(s):  
Girish R. Kale ◽  
Xingbo Yang ◽  
Jean-Marc Philippe ◽  
Madhav Mani ◽  
Pierre-François Lenne ◽  
...  
Keyword(s):  
Myosin Ii ◽  
Epithelial Morphogenesis ◽  
Shear Stresses ◽  
Mechanical Forces ◽  
Mechanical Tension ◽  
Tensile Forces ◽  
Axis Elongation ◽  
Persistent Cell ◽  
Adhesive Forces ◽  
E Cadherin

AbstractDuring epithelial morphogenesis, cell contacts (junctions) are constantly remodeled by mechanical forces that work against adhesive forces. E-cadherin complexes play a pivotal role in this process by providing persistent cell adhesion and by transmitting mechanical tension. In this context, it is unclear how mechanical forces affect E-cadherin adhesion and junction dynamics.During Drosophila embryo axis elongation, Myosin-II activity in the apico-medial and junctional cortex generates mechanical forces to drive junction remodeling. Here we report that the ratio between Vinculin and E-cadherin intensities acts as a ratiometric readout for these mechanical forces (load) at E-cadherin complexes. Medial Myosin-II loads E-cadherin complexes on all junctions, exerts tensile forces, and increases levels of E-cadherin. Junctional Myosin-II, on the other hand, biases the distribution of load between junctions of the same cell, exerts shear forces, and decreases the levels of E-cadherin. This work suggests distinct effects of tensile versus shear stresses on E-cadherin adhesion.

scholarly journals Inhibition of a negative feedback for persistent epithelial cell–cell junction contraction by p21-activated kinase 3

2019 ◽  
Author(s):  
Hiroyuki Uechi ◽  
Erina Kuranaga
Keyword(s):  
Epithelial Cell ◽  
Negative Feedback ◽  
Myosin Ii ◽  
Cell Junction ◽  
Mechanical Forces ◽  
Tensile Forces ◽  
P21 Activated Kinase ◽  
Actin Protrusions ◽  
E Cadherin ◽  
Cell Cell

AbstractActin-mediated mechanical forces are central drivers of cellular dynamics. They generate protrusive and contractile dynamics, the latter of which are induced in concert with myosin II bundled at the site of contraction. These dynamics emerge concomitantly in tissues and even each cell; thus, the tight regulation of such bidirectional forces is important for proper cellular deformation. Here, we show that contractile dynamics can eventually disturb cell–cell junction contraction in the absence of p21-activated kinase 3 (Pak3). Upon Pak3 depletion, contractility induces the formation of abnormal actin protrusions at the shortening junctions, which reduces E-cadherin levels at adherens junctions. Such E-cadherin dilution dissociates myosin II from the contracting junctions, leading to a reduction in junctional tensile forces. Overexpressing E-cadherin restores the association of myosin II at the junctions and junction contraction. Our results suggest that contractility both induces and perturbs junction contraction and that the attenuation of such perturbations by Pak3 facilitates persistent junction shortening.

scholarly journals The force-sensitive protein Ajuba regulates cell adhesion during epithelial morphogenesis

2018 ◽  
Vol 217 (10) ◽  
pp. 3715-3730 ◽  
Author(s):  
William Razzell ◽  
Maria E. Bustillo ◽  
Jennifer A. Zallen
Keyword(s):  
Cell Adhesion ◽  
Adherens Junctions ◽  
The Body ◽  
Epithelial Morphogenesis ◽  
Mechanical Forces ◽  
Lim Domain ◽  
Lim Domains ◽  
High Tension ◽  
Axis Elongation ◽  
Epithelial Sheets

The reorganization of cells in response to mechanical forces converts simple epithelial sheets into complex tissues of various shapes and dimensions. Epithelial integrity is maintained throughout tissue remodeling, but the mechanisms that regulate dynamic changes in cell adhesion under tension are not well understood. In Drosophila melanogaster, planar polarized actomyosin forces direct spatially organized cell rearrangements that elongate the body axis. We show that the LIM-domain protein Ajuba is recruited to adherens junctions in a tension-dependent fashion during axis elongation. Ajuba localizes to sites of myosin accumulation at adherens junctions within seconds, and the force-sensitive localization of Ajuba requires its N-terminal domain and two of its three LIM domains. We demonstrate that Ajuba stabilizes adherens junctions in regions of high tension during axis elongation, and that Ajuba activity is required to maintain cell adhesion during cell rearrangement and epithelial closure. These results demonstrate that Ajuba plays an essential role in regulating cell adhesion in response to mechanical forces generated by epithelial morphogenesis.

scholarly journals Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Felix Spira ◽  
Sara Cuylen-Haering ◽  
Shalin Mehta ◽  
Matthias Samwer ◽  
Anne Reversat ◽  
...  
Keyword(s):  
Myosin Ii ◽  
Local Network ◽  
Polarization Microscopy ◽  
Cleavage Furrow ◽  
Mechanical Forces ◽  
Biological Processes ◽  
Actin Network ◽  
Animal Cells ◽  
Mechanical Tension ◽  
Cortical Tension

The actomyosin ring generates force to ingress the cytokinetic cleavage furrow in animal cells, yet its filament organization and the mechanism of contractility is not well understood. We quantified actin filament order in human cells using fluorescence polarization microscopy and found that cleavage furrow ingression initiates by contraction of an equatorial actin network with randomly oriented filaments. The network subsequently gradually reoriented actin filaments along the cell equator. This strictly depended on myosin II activity, suggesting local network reorganization by mechanical forces. Cortical laser microsurgery revealed that during cytokinesis progression, mechanical tension increased substantially along the direction of the cell equator, while the network contracted laterally along the pole-to-pole axis without a detectable increase in tension. Our data suggest that an asymmetric increase in cortical tension promotes filament reorientation along the cytokinetic cleavage furrow, which might have implications for diverse other biological processes involving actomyosin rings.

scholarly journals Rho GTPase and Shroom direct planar polarized actomyosin contractility during convergent extension

2014 ◽  
Vol 204 (4) ◽  
pp. 575-589 ◽  
Author(s):  
Sérgio de Matos Simões ◽  
Avantika Mainieri ◽  
Jennifer A. Zallen
Keyword(s):  
Rho Gtpase ◽  
Binding Protein ◽  
Myosin Ii ◽  
Rho Kinase ◽  
Actin Binding ◽  
Mechanical Forces ◽  
Convergent Extension ◽  
Planar Polarity ◽  
Axis Elongation ◽  
Actomyosin Contraction

Actomyosin contraction generates mechanical forces that influence cell and tissue structure. During convergent extension in Drosophila melanogaster, the spatially regulated activity of the myosin activator Rho-kinase promotes actomyosin contraction at specific planar cell boundaries to produce polarized cell rearrangement. The mechanisms that direct localized Rho-kinase activity are not well understood. We show that Rho GTPase recruits Rho-kinase to adherens junctions and is required for Rho-kinase planar polarity. Shroom, an asymmetrically localized actin- and Rho-kinase–binding protein, amplifies Rho-kinase and myosin II planar polarity and junctional localization downstream of Rho signaling. In Shroom mutants, Rho-kinase and myosin II achieve reduced levels of planar polarity, resulting in decreased junctional tension, a disruption of multicellular rosette formation, and defective convergent extension. These results indicate that Rho GTPase activity is required to establish a planar polarized actomyosin network, and the Shroom actin-binding protein enhances myosin contractility locally to generate robust mechanical forces during axis elongation.

The Role of Mechanical Tension in Neurons

2010 ◽  
Vol 1274 ◽  
Author(s):  
Taher Saif ◽  
Jagannathan Rajagopalan ◽  
Alireza Tofangchi
Keyword(s):  
Mechanical Response ◽  
Mechanical Forces ◽  
Active Tension ◽  
Mechanical Tension ◽  
Deformation Response ◽  
Linear Force ◽  
Tension Regulation ◽  
Over Time

AbstractWe used high resolution micromechanical force sensors to study the in vivo mechanical response of embryonic Drosophila neurons. Our experiments show that Drosophila axons have a rest tension of a few nN and respond to mechanical forces in a manner characteristic of viscoelastic solids. In response to fast externally applied stretch they show a linear force-deformation response and when the applied stretch is held constant the force in the axons relaxes to a steady state value over time. More importantly, when the tension in the axons is suddenly reduced by releasing the external force the neurons actively restore the tension, sometimes close to their resting value. Along with the recent findings of Siechen et al (Proc. Natl. Acad. Sci. USA 106, 12611 (2009)) showing a link between mechanical tension and synaptic plasticity, our observation of active tension regulation in neurons suggest an important role for mechanical forces in the functioning of neurons in vivo.

Mutant cadherin affects epithelial morphogenesis and invasion, but not transformation

2001 ◽  
Vol 114 (6) ◽  
pp. 1237-1246 ◽  
Author(s):  
M.L. Troxell ◽  
D.J. Loftus ◽  
W.J. Nelson ◽  
J.A. Marrs
Keyword(s):  
Tumor Progression ◽  
Mdck Cells ◽  
Collagen Gel ◽  
Collagen Matrix ◽  
Soft Agar ◽  
Epithelial Morphogenesis ◽  
Adhesion System ◽  
Severe Impairment ◽  
Hepatocyte Growth ◽  
E Cadherin

MDCK cells were engineered to reversibly express mutant E-cadherin protein with a large extracellular deletion. Mutant cadherin overexpression reduced the expression of endogenous E- and K-cadherins in MDCK cells to negligible levels, resulting in decreased cell adhesion. Despite severe impairment of the cadherin adhesion system, cells overexpressing mutant E-cadherin formed fluid-filled cysts in collagen gel cultures and responded to hepatocyte growth factor/scatter factor (HGF/SF) that induced cellular extension formation with a frequency similar to that of control cysts. However, cells were shed from cyst walls into the lumen and into the collagen matrix prior to and during HGF/SF induced tubule extension. Despite the propensity for cell dissociation, MDCK cells lacking cadherin adhesion molecules were not capable of anchorage-independent growth in soft agar and cell proliferation rate was not affected. Thus, cadherin loss does not induce transformation, despite inducing an invasive phenotype, a later stage of tumor progression. These experiments are especially relevant to tumor progression in cells with altered E-cadherin expression, particularly tumor samples with identified E-cadherin extracellular domain genomic mutations.

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