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Biochem J. 2015 Dec 15;472(3):339-52. doi: 10.1042/BJ20150410. Epub 2015 Oct 6.

Phosphoregulation of the C. elegans cadherin-catenin complex.

Author information

1
Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53706, U.S.A.
2
Department of Zoology and Program in Genetics, University of Wisconsin-Madison, Madison, WI 53706, U.S.A.
3
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, U.S.A.
4
Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53706, U.S.A. audhya@wisc.edu.

Abstract

Adherens junctions play key roles in mediating cell-cell contacts during tissue development. In Caenorhabditis elegans embryos, the cadherin-catenin complex (CCC), composed of the classical cadherin HMR-1 and members of three catenin families, HMP-1, HMP-2 and JAC-1, is necessary for normal blastomere adhesion, gastrulation, ventral enclosure of the epidermis and embryo elongation. Disruption of CCC assembly or function results in embryonic lethality. Previous work suggests that components of the CCC are subject to phosphorylation. However, the identity of phosphorylated residues in CCC components and their contributions to CCC stability and function in a living organism remain speculative. Using mass spectrometry, we systematically identify phosphorylated residues in the essential CCC subunits HMR-1, HMP-1 and HMP-2 in vivo. We demonstrate that HMR-1/cadherin phosphorylation occurs on three sites within its β-catenin binding domain that each contributes to CCC assembly on lipid bilayers. In contrast, phosphorylation of HMP-2/β-catenin inhibits its association with HMR-1/cadherin in vitro, suggesting a role in CCC disassembly. Although HMP-1/α-catenin is also phosphorylated in vivo, phosphomimetic mutations do not affect its ability to associate with other CCC components or interact with actin in vitro. Collectively, our findings support a model in which distinct phosphorylation events contribute to rapid CCC assembly and disassembly, both of which are essential for morphogenetic rearrangements during development.

KEYWORDS:

conformational change; recombinant protein expression; small-angle X-ray scattering (SAXS)

PMID:
26443865
PMCID:
PMC4663164
DOI:
10.1042/BJ20150410
[Indexed for MEDLINE]
Free PMC Article

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