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

ABSTRACT: In metazoan adherens junctions, ?-catenin links the cytoplasmic tail of classical cadherins to the F-actin-binding protein ?-catenin. Phosphorylation of a Ser/Thr-rich region in the cadherin tail dramatically enhances affinity for ?-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 ?-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 ?-catenin, which is also a transcriptional coactivator in Wnt signaling. Nematodes and planaria, however, have a set of paralogous ?-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.

SUBMITTER: Choi HJ 

PROVIDER: S-EPMC4390766 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature