Format

Send to

Choose Destination
J Biol Chem. 2017 Oct 6;292(40):16477-16490. doi: 10.1074/jbc.M117.795567. Epub 2017 Aug 25.

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

Author information

1
From the Program in Genetics.
2
Department of Zoology, and.
3
the Departments of Biological Sciences and.
4
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706.
5
Chemistry, Seoul National University, Seoul 08826, South Korea, and.
6
the Departments of Structural Biology and Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305.
7
From the Program in Genetics, choihj@snu.ac.kr.

Abstract

Stable tissue integrity during embryonic development relies on the function of the cadherin·catenin complex (CCC). The Caenorhabditis elegans CCC is a useful paradigm for analyzing in vivo 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 in vitro 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 in vitro. In vivo experiments using HMP-2 S47E and Y69E mutants showed that they are unable to rescue hmp-2(zu364) mutants, suggesting that phosphorylation of HMP-2 on Ser-47 and Tyr-69 could be important for regulating CCC formation in C. elegans 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.

KEYWORDS:

adherens junction; cadherin-catenin complex; crystal structure; morphogenesis; phosphoregulation; α-catenin; β-catenin

PMID:
28842483
PMCID:
PMC5633108
[Available on 2018-10-06]
DOI:
10.1074/jbc.M117.795567
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center