Skip to main content
Fig. 2 | Cell Communication and Signaling

Fig. 2

From: E-cadherin roles in animal biology: A perspective on thyroid hormone-influence

Fig. 2

Signaling pathways involved in cell-cell adhesion mediated by E-cadherin in physiological and pathological conditions. a Shortly after their synthesis, cadherins associate with β-catenin and phosphorylation on the RER avoid degradation of uncomplexed cadherins and the pro-region cleavage by furin proteases in the trans-Golgi network. When the cis E-cadherin surface pool increases, pro-domain cleavage induces dimerization, trans homophilic bonding and E-cadherin adhesive activity. Delivery of newly synthesized E-cadherin to the basolateral cell surface should be mediated by Rab 11, golgin-97, Sec5, 6, Protein Associated with Lin Seven 1 (PALS), aquaporin 3 (AQP3), p120-ctn, and possibly β-catenin, via localization at the centrosome. b AJs-disassembly by dysfunction of E-cadherin─catenin complexes (CCC) releases catenins that accumulate in the cytoplasm. β-catenins are then sequestered and phosphorylated by the adenomatous polyposis coli (APC)–axin–glycogen synthase kinase 3β (GSK-3β) complex, inducing their ubiquitination by the E3 ubiquitin-ligase βTrCP subunit for proteosomal degradation. However, if at the same time the Wnt signaling pathway is activated, GSK-3β is repressed and β-catenins are no longer phosphorylated and are translocated to the nucleus where their bind TCF/LEF1 transcription factors and modulate gene expression involved in cell proliferation and migration. Cytoplasmic p120-ctns detached from AJs, in turn, activate Rac1 and Cdc42 through Vav2 (Rho-GEF) and represse Rho, promoting filopodia and lamellipodia projections. PI3K is recruited to the membrane by intact E-cadherin adhesion junctions, where it generates PIP3. This activates Tiam1 (Rho-GEF) and subsequently Rac1 and Cdc42, sequestring the GTPase-activating protein (IQGAP1), avoiding IQGAP-binding to β-catenins, and displacing α-catenins from the CCCs, thereby disrupting the CCC-anchoring to the cytoskeleton. Thus, while the activation of Cdc42 and Rac1 induces the formation of filopodia and lamellipodia respectively, Rho induces the formation of actin stress fibers. Cytoplasmic p120-ctn also can translocate to the nucleus to associate with Kaiso and modulate gene expression

Back to article page