EPLIN mediates linkage of the cadherin–catenin complex to F-actin and stabilizes the circumferential actin belt

Abstract

The cadherin-catenin complex is the major machinery for cell-cell adhesion in many animal species. This complex in general associates with actin fibers at its cytoplasmic side, organizing the adherens junction (AJ). In epithelial cells, the AJ encircles the cells near their apical surface and forms the ''zonula adherens'' or ''adhesion belt.'' The mechanism as to how the cadherin-catenin complex and F-actin cooperate to generate these junctional structures, however, remains unknown. Here, we show that EPLIN (epithelial protein lost in neoplasm; also known as Lima-1), an actin-binding protein, couples with ␣-catenin and, in turn, links the cadherin-catenin complex to F-actin. Without EPLIN, this linkage was unable to form. When EPLIN had been depleted in epithelial cells, the adhesion belt was disorganized and converted into zipper-like junctions in which actin fibers were radially arranged. However, nonjunctional actin fibers were not particularly affected by EPLIN depletion. As EPLIN is known to have the ability to suppress actin depolymerization, our results suggest that EPLIN functions to link the cadherin-catenin complex to F-actin and simultaneously stabilizes this population of actin fibers, resulting in the establishment of the adhesion belt.adherens junction ͉ epithelial cells ͉ cell adhesion

E-cadherin is under constitutive actomyosin-generated tension that is increased at cell–cell contacts upon externally applied stretch

“…Therefore, the cadherin/catenin/actin linkage may be highly dynamic, or its components may require a specific conformation not recapitulated in vitro to bind actin. This linkage may also involve additional actin-binding proteins such as activated vinculin or epithelial protein lost in neoplasm (EPLIN), which bind to α-catenin (16)(17)(18)(19)(20)(21). In addition to actin, the classical cadherin/γ-catenin (plakoglobin) complex can also associate with intermediate filaments in some instances (22,23).…”

EMT, the cytoskeleton, and cancer cell invasion

“…The second population of actin is an underlying, dynamic actin framework to which the SAJs are linked and correctly positioned by α-catenin. One protein replacing α-catenin in the E-cadherin/β-catenin complex to SAJ could be eplin, a newly identified actin-binding protein [26]. The juxtamembrane domain of E-cadherin binds to p120-catenin which is important in surface tracking, lysosomal degradation and correct membrane localization of Ecadherin [27][28][29][30].…”

Adherens Junction: Molecular Architecture and Regulation

“…This finding suggested the possibility that the cadherin -b-catenin -a-catenin complex might interact with F-actin via some other mediator(s). In fact, a-catenin has been shown to associate with actin-binding proteins such as formin (Kobielak et al 2004) and vinculin (Watabe- Uchida et al 1998), and a very recent study identified another actin-binding protein, EPLIN (epithelial protein lost in neoplasm; also known as Lima-1), as an a-catenin partner (Abe and Takeichi 2008). EPLIN is known to enhance the bundling of actin filaments and to stabilize them by suppressing F-actin depolymerization (Maul et al 2003).…”

“…On the other hand, EPLIN loss in epithelia results in different types of defects at the junctions. The circumferential actin belt disappears, being converted to radially oriented actin filaments, indicating that EPLIN is important not only for the linkage between cadherin and F-actin but also for stabilizing this unique configuration of actin fibers (Abe and Takeichi 2008). Importantly, the actin filaments, rearranged as a result of EPLIN loss, still target cadherins, which now assume a spotty localization as seen in fibroblasts or immature epithelial junctions.…”