A Conserved Phosphorylation Switch Controls the Interaction between Cadherin and beta-Catenin In Vitro and In Vivo

作者：Choi Hee Jung^*; Loveless Timothy; Lynch Allison M; Bang Injin; Hardin Jeff; Weis William I

来源：Developmental Cell, 2015, 33(1): 82-93.

DOI：10.1016/j.devcel.2015.02.005

In metazoan adherens junctions, beta-catenin links the cytoplasmic tail of classical cadherins to the F-actin-binding protein a-catenin. Phosphorylation of a Ser/Thr-rich region in the cadherin tail dramatically enhances affinity for beta-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 beta-catenin homolog HMP-2. Ablation of this phosphoserine interaction produces developmental defects that resemble full loss-of- Hammerhead and Humpback) phenotypes. Most metazoans possess a single gene for beta-catenin, which is also a transcriptional coactivator in Wnt signaling. Nematodes and planaria, however, have a set of paralogous beta-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.

• 出版日期2015-4-6