Can 1000 Reviews Be Wrong? Actin, α-Catenin, and Adherens Junctions

ArticleinCell 123(5):769-72 · January 2006with11 Reads
DOI: 10.1016/j.cell.2005.11.009 · Source: PubMed
Coupling between cell adhesion and the actin cytoskeleton is thought to require a stable link between the cadherin-catenin complex and actin that is mediated by alpha-catenin. In this issue of Cell, the Weis and Nelson groups call this static model into question, showing that alpha-catenin can directly regulate actin dynamics (Drees et al., 2005 and Yamada et al., 2005).
    • "Adherens junctions form through homophilic interactions between E-cadherins whose cytoplasmic domains are associated with a filamentous actin belt through a large number of adaptor proteins (Abe and Takeichi, 2008). Recently, epithelial protein lost in neoplasm (EPLIN, also known as LIMA1) has been shown to serve as an adaptor in adherens junctions and to form a ternary complex with a-catenin and F-actin without impairing their binding to b-catenin (Gates and Peifer, 2005; Mège et al., 2006; Abe and Takeichi, 2008; Baum and Georgiou, 2011). "
    [Show abstract] [Hide abstract] ABSTRACT: PINCH1 is a LIM-only domain protein that forms a ternary complex with integrin-linked kinase (ILK) and parvin (IPP complex) downstream of integrins. Here we demonstrate that PINCH-1 gene ablation in the epidermis of mice caused epidermal detachment from the basement membrane, epidermal hyperthickening and progressive hair loss. PINCH-1 deficient keratinocytes also displayed profound adhesion, spreading and migration defects in vitro that were, however, significantly more severe than those of ILK-deficient keratinocytes indicating that PINCH-1 also exerts functions in an ILK-independent manner. By isolating the PINCH-1 interactome, the LIM domain containing and actin-binding protein Epithelial Protein Lost in Neoplasm (EPLIN) was identified as a novel PINCH-1 associated protein. EPLIN localized in a PINCH-1-dependent manner to integrin adhesion sites of keratinocytes in vivo and in vitro and its depletion severely attenuated keratinocyte spreading and migration on collagen and fibronectin without affecting PINCH-1 levels in FAs. Since the low PINCH-1 levels in ILK-deficient keratinocytes were sufficient to recruit EPLIN to integrin adhesions, our findings suggest that PINCH-1 regulates integrin-mediated adhesion of keratinocytes through the interactions with ILK as well as EPLIN.
    Article · Jan 2015
    • "In developing epithelial cells, cell–cell coupling occurs mainly at the apical adherens junctions through E-cadherin, via β-catenin and α-catenin (Halbleib and Nelson, 2006). Although the exact molecular composition of this force transmitting complex has been controversial (Gates and Peifer, 2005; Yamada et al., 2005), recent evidence suggests that α-catenin can undergo force dependent conformational changes that reveal vinculin binding sites to strengthen the linkage of the cadherin/catenin complex with actin filaments (Leerberg et al., 2014; Yao et al., 2014; Yonemura et al., 2010). In many tissues, this can be seen in stress-bearing actomyosin cables that cross cell–cell boundaries (Landsberg et al., 2009; Monier et al., 2010; Röper, 2013 ). "
    [Show abstract] [Hide abstract] ABSTRACT: The shape of a single animal cell is determined both by its internal cytoskeleton and through physical interactions with its environment. In a tissue context, this extracellular environment is made up largely of other cells and the extracellular matrix. As a result, the shape of cells residing within an epithelium will be determined both by forces actively generated within the cells themselves and by their deformation in response to forces generated elsewhere in the tissue as they propagate through cell-cell junctions. Together these complex patterns of forces combine to drive epithelial tissue morphogenesis during both development and homeostasis. Here we review the role of both active and passive cell shape changes and mechanical feedback control in tissue morphogenesis in different systems.
    Full-text · Article · Jan 2015
    • "Other receptors such as syndecans, a collection of membrane-intercalated proteoglycans, work in synergy with integrins to provide cellular adhesion to their surrounding matrix [74]. Cadherin molecules facilitate cell–cell adhesion that in addition to influencing adhesion to the extracellular matrix can dictate cell behaviour and extracellular matrix production [75,76]. The availability of binding sites for cells to attach largely depends on the type of hydrogel. "
    [Show abstract] [Hide abstract] ABSTRACT: The development of hydrogel-based biomaterials represents a promising approach to generating new strategies for tissue engineering and regenerative medicine. In order to develop more sophisticated cell-seeded hydrogel constructs, it is important to understand how cells mechanically interact with hydrogels. In this paper, we review the mechanisms by which cells remodel hydrogels, the influence that the hydrogel mechanical and structural properties have on cell behaviour and the role of mechanical stimulation in cell-seeded hydrogels. Cell-mediated remodelling of hydrogels is directed by several cellular processes, including adhesion, migration, contraction, degradation and extracellular matrix deposition. Variations in hydrogel stiffness, density, composition, orientation and viscoelastic characteristics all affect cell activity and phenotype. The application of mechanical force on cells encapsulated in hydrogels can also instigate changes in cell behaviour. By improving our understanding of cell-material mechano-interactions in hydrogels, this should enable a new generation of regenerative medical therapies to be developed.
    Article · Apr 2014
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