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PhD Exit Seminar – Luka Sheppard (Tepass Lab)

July 22 @ 2:10 pm - 3:00 pm

The M-Region of α-Catenin Cooperates with Canoe, Ajuba, Vinculin and α-Actinin to Support Adhesion During Drosophila Embryonic Morphogenesis

 

Abstract

α-Catenin is a core component of the cadherin-catenin adhesion complex that couples cadherin to the actin cytoskeleton. The mechanosensitive α-Catenin M-region is thought to recruit F-actin binding partners such as Vinculin under application of force to support adherens junctions (AJs). However, the function of M-region mechanosensing and its cooperation with binding partners to support dynamic adhesion in vivo remains unclear. Actomyosin contraction stretches the M-region into an open conformation, revealing cryptic binding sites and recruiting Vinculin. Whereas the loss of α-Catenin compromises adhesion and morphogenesis, null mutants for the α-Catenin-binding partners Vinculin, α-Actinin and Ajuba complete embryogenesis with no or minimal defects. Furthermore, the contribution of the M-region to recruitment of the only reported binding partner with any strong adhesion phenotype, Afadin/Canoe, has not been explored in vivo. Here we report an essential requirement for the M-region to epithelial integrity during Drosophila morphogenesis. We determine the distinct contributions of the M-region subdomains, M1, M2 and M3, with M2 making the major contribution to adhesion. M2 is required for the mechanosensitive enrichment of Ajuba, and together with M3 supports Canoe recruitment to tricellular junctions and reinforces AJs. In contrast, M1 negatively regulates adhesion through its inhibition of Ajuba recruitment and possibly through recruitment of α-Actinin. M1 also recruits Vinculin, which supports E-cadherin and adhesion at high tension edges. However, we find this role to be subtle – ultimately dispensable for adhesion. We also found that the M1-Vinculin interaction is redundant with Canoe, and a striking genetic interaction between the M-region and Canoe, together suggesting that Canoe and the M-region act in parallel to support AJs. Our data clarify the function of the cadherin-actin interface and argue that α-Catenin and its interaction partners are part of a cooperative and redundant network that supports AJs remodelling in embryogenesis.

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Join Zoom Meeting

https://us02web.zoom.us/j/85720950715?pwd=ZnJjUXdWMnBCcm4wTldPdU9Zcm5pQT09

Meeting ID: 857 2095 0715

Host: Ulrich Tepass (u.tepass@utoronto.ca)

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Details

Date:
July 22
Time:
2:10 pm - 3:00 pm
Event Tags:

Venue

Virtual