Patterns in Space: Coordinating Adhesion and Actomyosin Contractility at E-cadherin Junctions

Cadherin adhesion receptors are fundamental determinants of tissue organization in health and disease. Increasingly, we have come to appreciate that classical cadherins exert their biological actions through active cooperation with the contractile actin cytoskeleton. Rather than being passive resistors of detachment forces, cadherins can regulate the assembly and mechanics of the contractile apparatus itself. Moreover, coordinate spatial patterning of adhesion and contractility is emerging as a determinant of morphogenesis. Here we review recent developments in cadherins and actin cytoskeleton cooperativity, by focusing on E-cadherin adhesive patterning in the epithelia. Next, we discuss the underlying principles of cellular rearrangement during Drosophila germband extension and epithelial cell extrusion, as models of how planar and apical-lateral patterns of contractility organizes tissue architecture.Comment: 11 pages, 5 figures, PREVIEW OF PREPRINT ONL

Editorial overview: Membrane traffic and cell polarity

No abstract available

Cycling Rho for tissue contraction

Cell contractility, driven by the RhoA GTPase, is a fundamental determinant of tissue morphogenesis. In this issue, Mason et al. (2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201603077) reveal that cyclic inactivation of RhoA, mediated by its antagonist, C-GAP, is essential for effective contractility to occur

Contact inhibition of locomotion and mechanical cross-talk between cell-cell and cell-substrate adhesion determines the pattern of junctional tension in epithelial cell aggregates

We generated a computational approach to analyze the biomechanics of epithelial cell aggregates, either island or stripes or entire monolayers, that combines both vertex and contact-inhibition-of-locomotion models to include both cell-cell and cell-substrate adhesion. Examination of the distribution of cell protrusions (adhesion to the substrate) in the model predicted high order profiles of cell organization that agree with those previously seen experimentally. Cells acquired an asymmetric distribution of basal protrusions, traction forces and apical aspect ratios that decreased when moving from the edge to the island center. Our in silico analysis also showed that tension on cell-cell junctions and apical stress is not homogeneous across the island. Instead, these parameters are higher at the island center and scales up with island size, which we confirmed experimentally using laser ablation assays and immunofluorescence. Without formally being a 3-dimensional model, our approach has the minimal elements necessary to reproduce the distribution of cellular forces and mechanical crosstalk as well as distribution of principal stress in cells within epithelial cell aggregates. By making experimental testable predictions, our approach would benefit the mechanical analysis of epithelial tissues, especially when local changes in cell-cell and/or cell-substrate adhesion drive collective cell behavior.Comment: 39 pages, 8 Figures. Supplementary Information is include

Traffic control: p120-catenin acts as a gatekeeper to control the fate of classical cadherins in mammalian cells

Proteins of the p120 family have been implicated in the regulation of cadherin-based cell adhesion, but their relative importance in this process and their mechanism of action have remained less clear. Three papers in this issue suggest that p120 plays a key role in maintaining normal levels of cadherin in mammalian cells, and that it may do so by regulating cadherin trafficking (Chen et al., 2003; Davis et al., 2003; Xiao et al., 2003)

Doing cell biology in embryos: regulated membrane traffic and its implications for cadherin biology

Regulated trafficking of cadherin adhesion molecules is often invoked as a mechanism to generate dynamic adhesive cell-cell contacts for tissue modeling and morphogenesis. The past 2-3 years have seen several important papers that tackle the cell biology of cadherin trafficking in organismal systems to provide new insights into both mechanism and morphogenetic impact

Activity-driven relaxation of the cortical actomyosin II network synchronizes Munc18-1-dependent neurosecretory vesicle docking

In neurosecretory cells, secretory vesicles (SVs) undergo Ca2(+)-dependent fusion with the plasma membrane to release neurotransmitters. How SVs cross the dense mesh of the cortical actin network to reach the plasma membrane remains unclear. Here we reveal that, in bovine chromaffin cells, SVs embedded in the cortical actin network undergo a highly synchronized transition towards the plasma membrane and Munc18-1-dependent docking in response to secretagogues. This movement coincides with a translocation of the cortical actin network in the same direction. Both effects are abolished by the knockdown or the pharmacological inhibition of myosin II, suggesting changes in actomyosin-generated forces across the cell cortex. Indeed, we report a reduction in cortical actin network tension elicited on secretagogue stimulation that is sensitive to myosin II inhibition. We reveal that the cortical actin network acts as a 'casting net' that undergoes activity-dependent relaxation, thereby driving tethered SVs towards the plasma membrane where they undergo Munc18-1-dependent docking

Direct cadherin-activated cell signaling: a view from the plasma membrane

Classical cadherin adhesion molecules are key determinants of cell recognition and tissue morphogenesis, with diverse effects on cell behavior. Recent developments indicate that classical cadherins are adhesion-activated signaling receptors. In particular, early–immediate Rac signaling is emerging as a mechanism to coordinate cadherin–actin integration at the plasma membrane

Neogenin recruitment of the WAVE regulatory complex maintains adherens junction stability and tension

To maintain tissue integrity during epithelial morphogenesis, adherens junctions (AJs) must resist the mechanical stresses exerted by dynamic tissue movements. Junctional stability is dependent on actomyosin contractility within the actin ring. Here we describe a novel function for the axon guidance receptor, Neogenin, as a key component of the actin nucleation machinery governing junctional stability. Loss of Neogenin perturbs AJs and attenuates junctional tension. Neogenin promotes actin nucleation at AJs by recruiting the Wave regulatory complex (WRC) and Arp2/3. A direct interaction between the Neogenin WIRS domain and the WRC is crucial for the spatially restricted recruitment of the WRC to the junction. Thus, we provide the first example of a functional WIRS-WRC interaction in epithelia. We further show that Neogenin regulates cadherin recycling at the AJ. In summary, we identify Neogenin as a pivotal component of the AJ, where it influences both cadherin dynamics and junctional tension

Live imaging molecular changes in junctional tension upon VE-cadherin in zebrafish

Forces play diverse roles in vascular development, homeostasis and disease. VE-cadherin at endothelial cell-cell junctions links the contractile acto-myosin cytoskeletons of adjacent cells, serving as a tension-transducer. To explore tensile changes across VE-cadherin in live zebrafish, we tailored an optical biosensor approach, originally established in vitro. We validate localization and function of a VE-cadherin tension sensor (TS) in vivo. Changes in tension across VE-cadherin observed using ratio-metric or lifetime FRET measurements reflect acto-myosin contractility within endothelial cells. Furthermore, we apply the TS to reveal biologically relevant changes in VE-cadherin tension that occur as the dorsal aorta matures and upon genetic and chemical perturbations during embryonic development