Dynamic and static interactions between p120 catenin and E-cadherin regulate the stability of cell-cell adhesion

Noboru Ishiyama ¹, Seung-Hye Lee , Shuang Liu

⁰Division of Signaling Biology, Ontario Cancer Institute, ON, Canada.

Cell +

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April 8, 2010

View abstract on PubMed

Summary

p120 catenin (p120) binding to E-cadherin

Area Of Science

Cell adhesion
Molecular biology
Structural biology

Background

Cadherin-catenin complexes are vital for cell-cell adhesion stability.
p120 catenin (p120) association with the cadherin juxtamembrane domain (JMD) is critical for this stability.
Understanding this interaction is key to deciphering cellular processes like synapse development.

Purpose Of The Study

To elucidate the structural basis of p120 binding to the E-cadherin JMD.
To investigate the functional consequences of disrupting this interaction on cell adhesion and neuronal morphogenesis.
To understand how p120 regulates cadherin stability through distinct binding sites.

Main Methods

X-ray crystallography to determine the structure of p120 isoform 4A bound to the E-cadherin JMD(core).
Site-directed mutagenesis to alter p120 binding sites and assess effects on cadherin interaction in vitro and in cells.
Nuclear Magnetic Resonance (NMR) spectroscopy to study p120-JMD interactions and dynamics.
Cellular assays to evaluate the role of p120 mutations in neuronal dendritic spine morphogenesis.

Main Results

The crystal structure reveals modular binding pockets in p120 that are complementary to the E-cadherin JMD(core).
Specific p120 mutations disrupted binding to E-cadherin and N-cadherin, impacting cell adhesion.
These mutations allowed differentiation of N-cadherin-dependent and -independent steps in dendritic spine morphogenesis.
NMR studies indicated p120 associates with the JMD, influencing endocytosis and ubiquitination sites.

Conclusions

p120 catenin stabilizes cadherin-mediated cell-cell adhesion through specific interactions with the JMD.
p120's binding sites regulate cadherin stability by shielding critical residues involved in endocytosis and ubiquitination.
Disrupting p120-cadherin interaction provides insights into the molecular mechanisms of synapse development.

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