Mutational analysis supports a core role forDrosophilaα-Catenin in adherens junction function

Abstract

Summary a-catenin associates the cadherin-catenin complex with the actin cytoskeleton. a-catenin binds to b-catenin, which links it to the cadherin cytoplasmic tail, and F-actin, but also to a multitude of actin-associated proteins. These interactions suggest a highly complex cadherin-actin interface. Moreover, mammalian aE-catenin has been implicated in a cadherin-independent cytoplasmic function in Arp2/3-dependent actin regulation, and in cell signaling. The function and regulation of individual molecular interactions of a-catenin, in particular during development, are not well understood. We have generated mutations in Drosophila a-Catenin (a-Cat) to investigate a-Catenin function in this model, and to establish a setup for testing a-Catenin-related constructs in a-Cat-null mutant cells in vivo. Our analysis of a-Cat mutants in embryogenesis, imaginal discs and oogenesis reveals defects consistent with a loss of cadherin function. Compromising components of the Arp2/3 complex or its regulator SCAR ameliorate the a-Cat loss-of-function phenotype in embryos but not in ovaries, suggesting negative regulatory interactions between a-Catenin and the Arp2/3 complex in some tissues. We also show that the a-Cat mutant phenotype can be rescued by the expression of a DE-cadherin::a-Catenin fusion protein, which argues against an essential cytosolic, cadherin-independent role of Drosophila a-Catenin.

Tuning Collective Cell Migration by Cell–Cell Junction Regulation

“…A network of transcription factors, including Jing, SIX4, Yan, Similar (also known as HIF1a), Hindsight (HNT), and Jun-related antigen, is activated and controls the levels of DE-cadherin during border cell delamination and migration (Montell et al 2012). Levels of DE-cadherin need to be precisely regulated and deviations impair border cell migration; consequently, after initially reducing DE-cadherin levels during delamination, moving border cell clusters still maintain substantial levels of both DE-cadherin and its binding partner armadillo (b-catenin) between neighboring border cells to maintain collective migration as a cluster (Peifer 1993;Niewiadomska et al 1999;Sarpal et al 2012).…”

Structural Determinants of the Mechanical Stability of α-Catenin

“…Therefore, subsequent investigations of the structural elements determining the stability of the autoinhibited conformation focused on the central M region. The C-terminal domain is known to be required for actin anchorage and force transmission across the protein (24,26,57). In experiments, C-terminal domain deletion prevented ␣-catenin localization at the membrane (24,26,57).…”

“…The C-terminal domain is known to be required for actin anchorage and force transmission across the protein (24,26,57). In experiments, C-terminal domain deletion prevented ␣-catenin localization at the membrane (24,26,57). This result suggested cooperativity between the N-and C-terminal domains, but recent findings do not support this interpretation (39).…”

An Autoinhibited Structure of α-Catenin and Its Implications for Vinculin Recruitment to Adherens Junctions

“…Their critical role in cell adhesion is underscored by pathological consequences of deletion or truncation of ␣-catenin genes in mammals, such as cancer metastasis (7), cerebellar hypoplasia (8), and arrhythmogenic cardiomyopathy (9). As well, the embryonic lethality has been reported for ␣-catenin-null flies (10). Cell biology studies revealed that ␣E-catenin is essential for organization of the apical junctional complex (AJC) (11), containing tight junction and AJ, by forming two types of AJs, punctum adherens and zonula adherens, in polarized epithelial cell monolayer (supplemental Fig.…”