Dynamic and static interactions between p120 catenin and E-cadherin regulate the stability of cell-cell adhesion.
The association of p120 catenin (p120) with the juxtamembrane domain (JMD) of the cadherin cytoplasmic tail is critical for the surface stability of cadherin-catenin cell-cell adhesion complexes. Here, we present the crystal structure of p120 isoform 4A in complex with the JMD core region (JMD(core)) of E-cadherin. The p120 armadillo repeat domain contains modular binding pockets that are complementary to electrostatic and hydrophobic properties of the JMD(core). Single-residue mutations within the JMD(core)-binding site of p120 abolished its interaction with E- and N-cadherins in vitro and in cultured cells. These mutations of p120 enabled us to clearly differentiate between N-cadherin-dependent and -independent steps of neuronal dendritic spine morphogenesis crucial for synapse development. NMR studies revealed that p120 regulates the stability of cadherin-mediated cell-cell adhesion by associating with the majority of the JMD, including residues implicated in clathrin-mediated endocytosis and Hakai-dependent ubiquitination of E-cadherin, through its discrete "dynamic" and "static" binding sites.
Ishiyama
Noboru
N
Division of Signaling Biology, Ontario Cancer Institute, ON, Canada.
Lee
Seung-Hye
SH
Liu
Shuang
S
Li
Guang-Yao
GY
Smith
Matthew J
MJ
Reichardt
Louis F
LF
Ikura
Mitsuhiko
M
D000818:Animals; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051177:Catenins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D011993:Recombinant Fusion Proteins; D000095002:Delta Catenin