Cell–cell adhesion in metazoans relies on evolutionarily conserved features of the α-catenin·β-catenin–binding interface

Abstract

Stable tissue integrity during embryonic development relies on the function of the cadherin·catenin complex (CCC). The CCC is a useful paradigm for analyzing requirements for specific interactions among the core components of the CCC, and it provides a unique opportunity to examine evolutionarily conserved mechanisms that govern the interaction between α- and β-catenin. HMP-1, unlike its mammalian homolog α-catenin, is constitutively monomeric, and its binding affinity for HMP-2/β-catenin is higher than that of α-catenin for β-catenin. A crystal structure shows that the HMP-1·HMP-2 complex forms a five-helical bundle structure distinct from the structure of the mammalian α-catenin·β-catenin complex. Deletion analysis based on the crystal structure shows that the first helix of HMP-1 is necessary for binding HMP-2 avidly and for efficient recruitment of HMP-1 to adherens junctions in embryos. HMP-2 Ser-47 and Tyr-69 flank its binding interface with HMP-1, and we show that phosphomimetic mutations at these two sites decrease binding affinity of HMP-1 to HMP-2 by 40-100-fold experiments using HMP-2 S47E and Y69E mutants showed that they are unable to rescue () mutants, suggesting that phosphorylation of HMP-2 on Ser-47 and Tyr-69 could be important for regulating CCC formation in Our data provide novel insights into how cadherin-dependent cell-cell adhesion is modulated in metazoans by conserved elements as well as features unique to specific organisms.

The adhesion modulation domain ofCaenorhabditis elegansα-catenin regulates actin binding during morphogenesis

“…We next investigated the function of HMP-1::GFP lacking the AMD. HMP-1ΔAMD::GFP localized to junctions in a manner indistinguishable from full-length HMP-1::GFP in a wild-type background, indicating that an intact N-terminal HMP-2/β-catenin–binding domain (Shao et al , 2017) is sufficient to target HMP-1ΔAMD::GFP to junctions. HMP-1ΔAMD::GFP rescues hmp-1(jc48) mutants, although poorly relative to HMP-1FL::GFP.…”

“…Strains were made by DNA microinjection: 1 ng/μl of the transgene of interest, in addition to 20 ng/μl noncoding DNA (F35D3) and 79 ng/μl rol-6(su1006) , was injected into the gonads of N2, as described previously (Mello and Fire, 1995). Comparable expression of all transgenes was confirmed using methods described previously (Shao et al , 2017).…”

Analysis of a vinculin homolog in a sponge (phylum Porifera) reveals that vertebrate-like cell adhesions emerged early in animal evolution

“…␣-Catenin family proteins have a similar structure but lack domains 2A and 2B (75). In ␣-catenin, domain 1A (also called N I ) binds to ␤-catenin (69,76,77) and in mammals is the site for homodimerization, which occludes ␤-catenin binding (69,75). In vinculin, domain 1A binds talin and mediates autoinhibition of F-actin binding.…”

Effects of Enteromyxum spp. (Myxozoa) infection in the regulation of intestinal E‐cadherin: Turbot against gilthead sea bream

“…However, it is difficult to identify them because they are often atypical or inconspicuous (Gruhl & Okamura, ). In addition, it is still unclear how junctions can be formed between cells of different species, given the complexity and specificity of the formation of cell junctions in an organism (Cavey & Lecuit, ; Shao et al, ). Furthermore, in an infection scenario, the parasite might exploit the host cells' capabilities to form junctions to subvert the defence response or simply to gain purchase of the host, as well as the host may alter the structure of its cell junctions to prevent formation of junctions with parasite cells (Gruhl & Okamura, ).…”