Transition of responsive mechanosensitive elements from focal adhesions to adherens junctions on epithelial differentiation

Abstract

The skin’s epidermis is a multilayered epithelial tissue and the first line of defense against mechanical stress. Its barrier function depends on an integrated assembly and reorganization of cell–matrix and cell–cell junctions in the basal layer and on different intercellular junctions in suprabasal layers. However, how mechanical stress is recognized and which adhesive and cytoskeletal components are involved are poorly understood. Here, we subjected keratinocytes to cyclic stress in the presence or absence of intercellular junctions. Both states not only recognized but also responded to strain by reorienting actin filaments perpendicular to the applied force. Using different keratinocyte mutant strains that altered the mechanical link of the actin cytoskeleton to either cell–matrix or cell–cell junctions, we show that not only focal adhesions but also adherens junctions function as mechanosensitive elements in response to cyclic strain. Loss of paxillin or talin impaired focal adhesion formation and only affected mechanosensitivity in the absence but not presence of intercellular junctions. Further analysis revealed the adherens junction protein α-catenin as a main mechanosensor, with greatest sensitivity conferred on binding to vinculin. Our data reveal a mechanosensitive transition from cell–matrix to cell–cell adhesions on formation of keratinocyte monolayers with vinculin and α-catenin as vital players.

aPKCi triggers basal extrusion of luminal mammary epithelial cells by tuning contractility and vinculin localization at cell junctions

“…Our data suggest that vinculin may switch between cell junctions and focal adhesions in an aPKCi-dependent manner. To date, it is not known whether vinculin can shuttle between cell–cell junctions and focal adhesions (40). Vinculin shuttling from cell–cell junctions to focal adhesion sites may not only control cell extrusion, but also promote efficient collective tumor cell invasion by affecting the dynamics of focal adhesions (41–43).…”

Skin tape proteomics identifies pathways associated with transepidermal water loss and allergen polysensitization in atopic dermatitis

“…Loss of integrins occurs during keratinocyte differentiation and changes in actin cytoskeleton through the action of cytoplasmic proteins that control actin assembly have been proposed to be involved in signaling between extracellular matrix-bound integrins and cell nuclei. 53,54 Further studies are required to examine the role of altered GSN-regulated actin assembly/integrin signal transduction in AD skin in epidermal differentiation and skin barrier homeostasis.…”

Adhesion of Epithelial Cells to PNIPAm Treated Surfaces for Temperature-Controlled Cell-Sheet Harvesting

“… 9 As we are dealing with confluent but not overconfluent densities of MDCK II cells after 48 h, the height increase of the PNIPAm film upon temperature reduction might not only serve as an adhesion repeller but actually activate mechanosensitive signaling feedback loops as described for paxillin/talin or cross communication from cell–substrate to cell–cell contacts via α catenin and vinculin. 67 This also highlights the benefit of PMS usage, as vinculin was shown to be preserved when using PNIPAm for subculture over mechanical or chemical dissolution. 8 Thus after 48 h and in contrast to the early adhesion phase, cell–cell contact forces based on cadherins should dominate this culture phase.…”