Research Interest

Connections between the cytoskeleton and intercellular junctions profoundly influence cell shape and motility. It is becoming increasingly clear that in addition to structural functions, components of the adhesion apparatus also possess signalling capabilities. Recent studies suggest that proteins with such dual functions may provide the means to integrate changes in morphology and gene expression during tissue and organ development. Our research focuses on the molecular analysis of signalling through junction-associated proteins. In the previous years, we have defined the p120ctn family of armadillo related proteins that includes the prototype p120ctn, p0071, δ-catenin/NPRAP, ARVCF and the more distantly related plakophilins 1-3. 

Like armadillo, β-catenin and plakoglobin these proteins are involved in mediating cell cell adhesion. Interaction of p120ctn, ARVCF and p0071 with E-cadherin increases E-cadherin half life substantially indicating that these proteins are essential for cadherin stability. Thus, p120ctn proteins directly influence adhesive strength by controlling the amount of cadherin available for adhesion at the cell surface. While classical cadherins are stabilized by the close p120ctn family members ARVCF, δ-catenin, and p0071, the more distantly related plakophilins do not localize at adherens junctions and do not interact with classical cadherins. Instead, they bind to desmosomal cadherins. Recent evidence suggests that plakophilins are essential components of the desmosomal plaque where they interact with desmosomal cadherins as well as the cytoskeletal linker protein desmoplakin. Plakophilins stabilize desmosomal proteins at the plasma membrane and therefore may function in a manner similar to p120ctn in the adherens junctions. 

Whereas adherens junctions localize to the tips of early membrane contacts, desmosomes form in the flanking regions that are already in apposition. P0071 has a unique function in junction assembly and stabilization since it is the only protein of the family that is able to interact with both classical cadherins and desmosomal proteins. High expression of p0071 favours cadherin stabilization thus shifting the balance between adherens junctions and desmosomes. These data indicate that p0071 is not only involved in regulation of cadherin stability and cadherin clustering but has an additional and unique function in the cross talk between adherens junctions and desmosomes.

Besides their junctional localization the p120ctn-related proteins also reveal a cytoplasmic and nuclear localization. While their nuclear function is still enigmatic, major progress in understanding their cytoplasmic role has been made. Our recent research focus is to elucidate the signalling functions of these proteins.

We take multi-faceted experimental approaches to these problems including:

  • Biochemical approaches to define protein protein interactions
  • analysis of protein complex formation, regulation and function in whole cells 
  • state-of-the art light microscopy 
  • live cell imaging of cellular and subcellular protein dynamics
  • analysis of abnormalities in cellular and subcellular organization in disease state