Adherens junction proteins on the move—From the membrane to the nucleus in intestinal diseases

Abstract

The function and structure of the mammalian epithelial cell layer is maintained by distinct intercellular adhesion complexes including adherens junctions (AJs), tight junctions, and desmosomes. The AJ is most integral for stabilizing cell-cell adhesion and conserving the structural integrity of epithelial tissues. AJs are comprised of the transmembrane protein E-cadherin and cytoplasmic catenin cofactors (α, β, γ, and p120-catenin). One organ where malfunction of AJ is a major contributor to disease states is the mammalian intestine. In the intestine, cell-cell adhesion complexes work synergistically to maintain structural integrity and homeostasis of the epithelium and prevent its malfunction. Consequently, when AJ integrity is compromised in the intestinal epithelium, the ensuing homeostatic disruption leads to diseases such as inflammatory bowel disease and colorectal carcinoma. In addition to their function at the plasma membrane, protein components of AJs also have nuclear functions and are thus implicated in regulating gene expression and intracellular signaling. Within the nucleus, AJ proteins have been shown to interact with transcription factors such as TCF/LEF and Kaiso (ZBTB33), which converge on the canonical Wnt signaling pathway. The multifaceted nature of AJ proteins highlights their complexity in modulating homeostasis and emphasizes the importance of their subcellular localization and expression in the mammalian intestine. In this review, we summarize the nuclear roles of AJ proteins in intestinal tissues; their interactions with transcription factors and how this leads to crosstalk with canonical Wnt signaling; and how nuclear AJ proteins are implicated in intestinal homeostasis and disease.

Comprehensive analysis of human tissues reveals unique expression and localization patterns of HSF1 and HSF2

“…Signal transmission occurs through the translocation of proteins from the membrane compartment to the nucleus, where they act as transcriptional regulators. 50 We hypothesize that when localized at cell–cell adhesion sites, HSF2 monitors the integrity of cell adhesion contacts. Previously, we have found that in human osteosarcoma U2OS cells, silencing of HSF2 led to marked downregulation of genes encoding cadherin superfamily proteins forming adherens junctions.…”

Effect and mechanism of apelin on lipopolysaccharide induced acute pulmonary vascular endothelial barrier dysfunction

“…The inter endothelial cell junctions, the tight adhesion between endothelial cells and basement membrane, and the shape of endothelial cells play important roles in maintaining the stability and integrity of the endothelial barrier 15 . The adherens junctions consist of VE-cadherin and associated α-catenin, β-catenin and p120-catenin adhesion complexes 16 . VE-cadherin anchors to circumferential actin bundles (CABs) via α-catenin and β-catenin linker proteins thus making cell junctions to remain stable between them.…”

Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function

“…Moving up apically along the lateral membrane are the adherens junctions. The primary role for adherens junctions is to mediate cell–cell adhesion, as well as taking part in cell signalling and transcriptional regulation [ 12 ]. Like desmosomes, adherens junctions include a cadherin family member as an intercell adhesion component anchored in the cytoplasm by Armadillo proteins.…”

“…Moving up apically along the lateral membrane are the adherens junctions. The primary role for adherens junctions is to mediate cell-cell adhesion, as well as taking part in cell signalling and transcriptional regulation [12]. Like desmosomes, adherens junctions Transport via the transcellular pathways is the physiological route for nutrient absorption and it involves specific transporters, such as for amino acids, sugars, short-chain fatty acids (SCFAs) [5], or it can occur in a non-specific manner through endocytosis (transcytosis) [6].…”