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Dev Cell. 2015 Apr 6;33(1):82-93. doi: 10.1016/j.devcel.2015.02.005.

A conserved phosphorylation switch controls the interaction between cadherin and β-catenin in vitro and in vivo.

Author information

1
School of Biological Sciences, Seoul National University, Seoul 151-747, South Korea. Electronic address: choihj@snu.ac.kr.
2
Program in Cellular and Molecular Biology, University of Wisconsin, Madison, WI 53706, USA.
3
Department of Zoology, University of Wisconsin, Madison, WI 53706, USA.
4
School of Biological Sciences, Seoul National University, Seoul 151-747, South Korea.
5
Program in Cellular and Molecular Biology, University of Wisconsin, Madison, WI 53706, USA; Department of Zoology, University of Wisconsin, Madison, WI 53706, USA.
6
Departments of Structural Biology and of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: bill.weis@stanford.edu.

Abstract

In metazoan adherens junctions, β-catenin links the cytoplasmic tail of classical cadherins to the F-actin-binding protein α-catenin. Phosphorylation of a Ser/Thr-rich region in the cadherin tail dramatically enhances affinity for β-catenin and promotes cell-cell adhesion in cell culture systems, but its importance has not been demonstrated in vivo. Here, we identify a critical phosphorylated serine in the C. elegans cadherin HMR-1 required for strong binding to the β-catenin homolog HMP-2. Ablation of this phosphoserine interaction produces developmental defects that resemble full loss-of-function (Hammerhead and Humpback) phenotypes. Most metazoans possess a single gene for β-catenin, which is also a transcriptional coactivator in Wnt signaling. Nematodes and planaria, however, have a set of paralogous β-catenins; for example, C. elegans HMP-2 functions only in cell-cell adhesion, whereas SYS-1 mediates transcriptional activation through interactions with POP-1/Tcf. Our structural data define critical sequence differences responsible for the unique ligand specificities of these two proteins.

PMID:
25850673
PMCID:
PMC4390766
DOI:
10.1016/j.devcel.2015.02.005
[Indexed for MEDLINE]
Free PMC Article

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