Researchers uncover mechanism of protein complex maintaining cell polarity
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A team led by Prof. Wang Chao and Prof. Huang Chengdong from the University of Science and Technology of China (USTC) of the Chinese Academy of Sciences (CAS) revealed the molecular mechanism of E-cadherin- Ankyrin-G (AnkG) complex assembly and its function in maintaining lateral membrane polarity. Their work is published in Nature Communications.
Adhesion junction is crucial for the stability of the epithelial lateral membrane and the maintenance of cell polarity. E-cadherin is an essential cell-cell adhesion protein, with the canonical E-cadherin-β-catenin-α-catenin complex forming an important protein network connecting adhesion molecules to the cytoskeleton.
In addition, E-cadherin can also interact with the scaffold protein AnkG and be associated with the cytoskeleton through β-spectrin. However, the molecular basis for the formation of the E-cadherin-AnkG complex, its interaction with the canonical cadherin-catenin complex and the molecular mechanism by which this complex affects the cell polarity remain unclear.
To solve this mystery, the research team utilized biochemical and nuclear magnetic resonance (NMR) experiments to investigate the interaction between E-cadherin and the AnkG membrane binding module through multiple sites.
Unlike the known binding modes of E-cadherin-catenin protein complexes or Ankyrin protein complexes, E-cadherin-AnkG complex can form dynamic binding complexes with molar ratios ranging from 1:1 to 1:2.
The researchers further revealed the key role of hydrophobic interactions in mediating the complex assembly using site-specific mutations and liquid NMR titrations.
Meanwhile, systematic cell biology experiments demonstrated the crucial role of AnkG in the localization and stability of E-cadherin at cell lateral membranes, indicating that the synthesis of cell lateral membranes and the maintenance of cell polarity also depend on the E-cadherin-AnkG complex.
Finally, the researchers sorted out the relationship between the canonical E-cadherin-catenin complex and the E-cadherin-AnkG complex and discussed the role of dynamic binding mode in maintaining the stability of E-cadherin-AnkG complex and cell polarity.
The study integrates various research methods, including biochemistry, cell biology, biophysics, and chemical biology, to clarify the molecular mechanism of the dynamic assembly of E-cadherin-AnkG complex, thus providing new insights into the molecular basis of human diseases caused by gene mutations and dysfunctional protein complex assembly, particularly in the context of cancer progression.
More information: Chao Kong et al, Dynamic interactions between E-cadherin and Ankyrin-G mediate epithelial cell polarity maintenance, Nature Communications (2023). DOI: 10.1038/s41467-023-42628-1
Journal information: Nature Communications
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