Structural and functional characterization of Caenorhabditis elegans α-catenin reveals constitutive binding to β-catenin and F-actin

Abstract

Intercellular epithelial junctions formed by classical cadherins, β-catenin, and the actin-binding protein α-catenin link the actin cytoskeletons of adjacent cells into a structural continuum. These assemblies transmit forces through the tissue and respond to intracellular and extracellular signals. However, the mechanisms of junctional assembly and regulation are poorly understood. Studies of cadherin-catenin assembly in a number of metazoans have revealed both similarities and unexpected differences in the biochemical properties of the cadherin·catenin complex that likely reflect the developmental and environmental requirements of different tissues and organisms. Here, we report the structural and biochemical characterization of HMP-1, the α-catenin homolog, and compare it with mammalian α-catenin. HMP-1 shares overall similarity in structure and actin-binding properties, but displayed differences in conformational flexibility and allosteric regulation from mammalian α-catenin. HMP-1 bound filamentous actin with an affinity in the single micromolar range, even when complexed with the β-catenin homolog HMP-2 or when present in a complex of HMP-2 and the cadherin homolog HMR-1, indicating that HMP-1 binding to F-actin is not allosterically regulated by the HMP-2·HMR-1 complex. The middle ( M) domain of HMP-1 appeared to be less conformationally flexible than mammalian α-catenin, which may underlie the dampened effect of HMP-2 binding on HMP-1 actin-binding activity compared with that of the mammalian homolog. In conclusion, our data indicate that HMP-1 constitutively binds β-catenin and F-actin, and although the overall structure and function of HMP-1 and related α-catenins are similar, the vertebrate proteins appear to be under more complex conformational regulation.

Nonmuscle myosin IIA is involved in recruitment of apical junction components through activation of α-catenin

“…α-catenin consists of three domains ( Fig. 5 A) ( Ishiyama et al, 2013 ; Yao et al, 2014 ; Escobar et al, 2015 ; Kang et al, 2017 ). The N-terminal (N) domain binds to β-catenin.…”

Putting VE-cadherin into JAIL for junction remodeling

“…A protein chain consisting, in order, of VE-cadherin, β-catenin and one of the three α-catenin proteins (CTNNA1, CTNNA2 or CTNNA3) binds to the actin filament, while γ-catenin (Cowin et al, 1986) is linked to vimentin intermediate filaments (Valiron et al, 1996;Kowalczyk et al, 1998). α-Catenin can directly bind to actin filaments in a tension-dependent manner (catch bound association), as has been shown for α-E-catenin (CTNNA1) in the epithelium (Yonemura et al, 2010;Buckley et al, 2014;Ladoux et al, 2015;Kang et al, 2017), or might use a further linker protein such as the epithelial protein lost in neoplasm (EPLIN; also known as LIMA1) (Maul and Chang, 1999). EPLIN is an actinbinding protein with possible mechanosensitive functions (Maul et al, 2003;Abe and Takeichi, 2008;Sanders et al, 2010;Taguchi et al, 2011) that localizes at EC junctions and has been suggested to modulate angiogenesis (Chervin-Pétinot et al, 2012).…”

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

“…In contrast, D. melanogaster vinculin is nonessential (97), but constitutive activation caused the formation of abundant cytoplasmic adhesion complexes with talin, producing morphological defects and death (97,98). Biochemical differences between vertebrate and invertebrate ␣-catenin have been detailed elsewhere (40,99), but all ␣-catenins characterized to date bind ␤-catenin and F-actin at the AJ and developmental disruption of ␣-catenin leads to morphological abnormalities and death (80, 100 -102).…”