Molecular interactions between desmosomal cadherins

Area of Science:

• Cell biology
• Biochemistry
• Structural biology

Background:

• Desmocollins (Dscs) and desmogleins (Dsgs) are essential cell-adhesion molecules forming desmosome junctions.
• They share structural similarities with classical cadherins, like E-cadherin.
• Understanding their interactions is crucial for cell adhesion mechanisms.

Purpose of the Study:

• To characterize protein-protein interactions of desmosomal cadherin type 2 isoforms (Dsc2 and Dsg2).
• To investigate the role of calcium ions (Ca(2+)) in these interactions.
• To provide quantitative data on the strength of homophilic and heterophilic associations.

Main Methods:

• Recombinant expression of Dsg2(1-2) and Dsc2(1-2) in E. coli.
• Analytical ultracentrifugation
• Chemical cross-linking
• Circular dichroism (CD)
• Fluorescence spectroscopy
• BIAcore analysis

Main Results:

• Direct evidence of Ca(2+) binding to desmosomal cadherins was obtained.
• Dsc2(1-2) exhibits both homophilic interactions and heterophilic interactions with Dsg2(1-2).
• Dsg2(1-2) shows weaker homophilic association compared to Dsc2(1-2).
• Heterophilic interactions are Ca(2+)-dependent; Ca(2+)-dependence of homophilic association is less clear.
• Dsc2(1-2) functional properties resemble classical cadherins.

Conclusions:

• Dsc2(1-2) and Dsg2(1-2) form homodimers and heterodimers.
• Ca(2+) plays a significant role in mediating heterophilic interactions between Dsc2 and Dsg.
• Dsc2 exhibits functional similarities to classical cadherins, supported by sequence homology.