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

Journal Article · · Journal of Biological Chemistry
 [1];  [2];  [3];  [4]; ORCiD logo [4]; ORCiD logo [5]; ORCiD logo [2]; ORCiD logo [6]
  1. Univ. of Wisconsin, Madison, WI (United States). Dept. of Zoology, Program in Genetics
  2. Seoul National Univ. (Korea, Republic of). Biological Sciences
  3. Univ. of Wisconsin, Madison, WI (United States). Program in Genetics and Program in Cellular and Molecular Biology
  4. Seoul National Univ. (Korea, Republic of). Dept. of Chemistry
  5. Stanford Univ., CA (United States). School of Medicine, Dept. of Structural Biology and Molecular and Cellular Physiology
  6. Univ. of Wisconsin, Madison, WI (United States). Dept. of Zoology, Program in Genetics, and Program in Cellular and Molecular Biology
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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.

Research Organization:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-76SF00515; GM094663; GM114462; GM058038; NRF-2016R1A2B4013488; 2015K2A1A2070030
OSTI ID:
1425346
Journal Information:
Journal of Biological Chemistry, Vol. 292, Issue 40; ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular BiologyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 6 works
Citation information provided by
Web of Science

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Cited By (2)

Effects of Enteromyxum spp. (Myxozoa) infection in the regulation of intestinal E‐cadherin: Turbot against gilthead sea bream journal January 2020
Analysis of a vinculin homolog in a sponge (phylum Porifera) reveals that vertebrate-like cell adhesions emerged early in animal evolution journal June 2018

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59 BASIC BIOLOGICAL SCIENCES
adherens junction
α-catenin
β-catenin
crystal structure
morphogenesis
cadherin-catenin complex
phosphoregulation