Phosphoregulation of the <i>C. elegans</i> cadherin–catenin complex

Callaci, Sandhya; Morrison, Kylee; Shao, Xuemei; Schuh, Amber L.; Wang, Yueju; Yates, John R.; Hardin, Jeff; Audhya, Anjon

doi:10.1042/bj20150410

Cited by 16 publications

(20 citation statements)

References 45 publications

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“…S4, Table 3). The values of the radius of gyration (R g ) and the maximum particle size (D max ) were 42 and 150 Å, respectively, in agreement with an earlier study (23). Comparison of the SAXS-derived envelope of full-length HMP-1 to that of the HMP-1 "head" comprising the N and M domains indicated that the protruding stalk of the envelope likely corresponds to the C-terminal ABD (Fig.…”

Section: Overall Architecture Of Full-length Hmp-1supporting

confidence: 90%

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

Kang

Bang

Jin

et al. 2017

Journal of Biological Chemistry

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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.

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Section: Overall Architecture Of Full-length Hmp-1supporting

confidence: 90%

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

Kang

Bang

Jin

et al. 2017

Journal of Biological Chemistry

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“…Although endogenous phosphorylation has not yet been observed at HMP-2 Ser-47 or Tyr-69 (63), it may be extremely difficult to detect whether it is only required transiently during dynamic junctional remodeling. The observation that HMP-2(S47A)::GFP and HMP-2(Y69F)::GFP constructs exhibit different junctional dynamics from wild-type HMP-2::GFP is consistent with the possibility that HMP-2 is endogenously phosphorylated at these sites.…”

Section: Conserved Phosphorylatable Residues In ␤-Catenin Are Requirementioning

confidence: 99%

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

Shao

Kang²,

Loveless

et al. 2017

Journal of Biological Chemistry

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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.

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“…In vivo , constructs carrying identical phosphomimetic mutations rescue, but somewhat more weakly than wild-type transgenes. In contrast, perturbations of phosphosites identified in HMP-1 from embryonic extracts did not affect the ability of HMP-1 to bind actin or its comformation 26 . These results are similar to those in vertebrate tissue culture and Drosophila , which found only weak effects of numerous phosphosites in α-catenin 27 .…”

Section: A Conserved Phosphorylation Switch Controls the Cadherin/β-cmentioning

confidence: 67%

“…Independent assessment of binding affinities via reconstitution on liposomes confirms the work of Choi et al . showing that S1212 is crucial for HMR-1/HMP-2 association 26 .…”

Section: A Conserved Phosphorylation Switch Controls the Cadherin/β-cmentioning

confidence: 98%

“…Significantly, S1212 and downstream residues are phosphorylated in vivo as well, based on results of co-immunoprecipitation/mass spectrometry analysis performed by Callaci et al . 26 . Independent assessment of binding affinities via reconstitution on liposomes confirms the work of Choi et al .…”

Section: A Conserved Phosphorylation Switch Controls the Cadherin/β-cmentioning

confidence: 99%

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Getting to the core of cadherin complex function in Caenorhabditis elegans

Hardin

2015

F1000Res

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The classic cadherin-catenin complex (CCC) mediates cell-cell adhesion in metazoans. Although substantial insights have been gained by studying the CCC in vertebrate tissue culture, analyzing requirements for and regulation of the CCC in vertebrates remains challenging. Caenorhabditis elegans is a powerful system for connecting the molecular details of CCC function with functional requirements in a living organism. Recent data, using an “angstroms to embryos” approach, have elucidated functions for key residues, conserved across all metazoans, that mediate cadherin/β-catenin binding. Other recent work reveals a novel, potentially ancestral, role for the C. elegans p120ctn homologue in regulating polarization of blastomeres in the early embryo via Cdc42 and the partitioning-defective (PAR)/atypical protein kinase C (aPKC) complex. Finally, recent work suggests that the CCC is trafficked to the cell surface via the clathrin adaptor protein complex 1 (AP-1) in surprising ways. These studies continue to underscore the value of C. elegans as a model system for identifying conserved molecular mechanisms involving the CCC.

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Phosphoregulation of the C. elegans cadherin–catenin complex

Cited by 16 publications

References 45 publications

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

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

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

Getting to the core of cadherin complex function in Caenorhabditis elegans

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