Figure 19–10 The linkage of classical cadherins to actin filaments. the cadherins are coupled indirectly to actin filaments through an adaptor protein complex containing p120-catenin, β-catenin, and α-catenin. Other proteins, including vinculin, associate with α-catenin and help provide the linkage to actin. β-Catenin has a second, and very important, function in intracellular signaling, as we discuss in Chapter 15 (see Figure 15–60). For clarity, this diagram does not show the cadherin of the adjacent cell in the junction.
(A) (B) recruitment of more (C) contractile actin and the disassembly of many adherens junctions. Furthermore, the contractile forces acting on a junction in one cell are balanced by contractile forces at the junction of the opposite cell, so that no cell pulls others toward it and thereby disrupts the uniform distribution of cells in the tissue.
We do not understand the mechanisms responsible for maintaining this balance. Adherens junctions seem to sense the forces acting on them and modify local actin and myosin behavior to balance the forces on both sides of the junction. Evidence for these mechanisms comes from studies of pairs of cultured mammalian cells connected by adherens junctions. If contractile activity in one cell is increased experimentally, the adherens junctions linking the two cells increase in size, and the contractile activity of the second cell increases to match that of the first—resulting in a balance of forces across the junction. These and other experiments suggest that adherens junctions are not simply passive sites of protein–protein binding but are dynamic tension sensors that regulate their behavior in response to changing mechanical conditions. This ability to transduce a mechanical signal into a change in junctional behavior is an example of mechanotransduction. We will see later that it is also important at cell–matrix junctions.
The mechanotransduction at cell–cell junctions is thought to depend, at least in part, on proteins in the cadherin complex that alter their shape when stretched by tension. The protein α-catenin, for example, is stretched from a folded to an extended conformation when contractile activity increases at the junction. The unfolding exposes a cryptic binding site for another protein, vinculin, which promotes the recruitment of more actin to the junction (Figure 19–12). By mechanisms such as this, pulling on a junction makes it stronger. Furthermore, as noted above, pulling on a junction in one cell will increase the contractile force generated in the attached cell.
In some cell types, actin contractility reduces cell–cell adhesion, particularly if large forces are involved. Large actin-based contractile forces might, in some tissues, pull sufficiently hard on the edges of cell–cell adhesions to peel them apart, particularly if contraction is coupled to additional regulatory mechanisms that weaken the adhesion. This mechanism might be important in certain forms of tissue remodeling during development, as we describe next.
tissue remodeling Depends on the Coordination of actin-Mediated Contraction With Cell–Cell adhesion
Adherens junctions are an essential part of the machinery for modeling the shapes of multicellular structures in the animal body. By indirectly linking the actin filaments in one cell to those in its neighbors, they enable the cells in the tissue to use their actin cytoskeletons in a coordinated way.
Adherens junctions occur in various forms. In many nonepithelial tissues, they appear as small punctate or linear attachments that connect the cortical