The function of α-Catenin mechanosensing in tissue morphogenesis

Abstract

α-catenin couples the cadherin-catenin complex to the actin cytoskeleton. The mechanosensitive α-catenin M region undergoes conformational changes upon application of force to recruit binding partners. Here, we took advantage to the tension landscape in the Drosophila embryo to define three different states of α-catenin mechanosensing in support of cell adhesion. Low, medium, and high tension contacts showed α-catenin M region-dependent low, medium, and high levels of Vinculin and Ajuba recruitment. In contrast, Afadin/Canoe acts in parallel to α-catenin at bicellular low and medium tension junctions, but requires an interaction with α-catenin for its tension-sensitive enrichment at high-tension tricellular junctions. Individual M region domains make complex contributions to cell adhesion through their impact on binding partner recruitment, and redundancies with the function of Afadin/Canoe. Our data argue that α-catenin and its interaction partners are part of a cooperative and partially redundant, mechanoresponsive network that supports AJs remodelling during morphogenesis.

Multivalent interactions make adherens junction–cytoskeletal linkage robust during morphogenesis

“…They examined the role of αcat’s middle domain, which opens up when tension is applied to junctions. Their data suggest that proteins recruited to the open conformation, including Ajuba, Vinculin, α-Actinin, and Cno itself, act in parallel with Cno in reinforcing junctions under tension ( Sheppard and Tepass, 2021 Preprint ).…”

Powering morphogenesis: multiscale challenges at the interface of cell adhesion and the cytoskeleton

“…, 2019 ; Perez-Vale et al. , 2021 ; Sheppard and Tepass, 2021 ). The field is beginning to use genetic approaches to explore the effects of removing individual protein–protein interactions on AJ stability during cell shape changes and rearrangements, often with surprising results.…”

“…Some interactions are critical, while others are largely redundant, leading to minor or tissue-specific defects in AJs challenged by shape change or remodeling (e.g., Yu and Zallen, 2020 ; Perez-Vale et al. , 2021 ; Sheppard and Tepass, 2021 ). Analyses like these will provide insights into one potential underlying principle explaining redundancy: that multivalent interactions between proteins in the network mean that disrupting one protein interaction leaves others intact, allowing retention of a functional AJ–cytoskeletal linkage.…”