Project information
Structural insights into the function of the key planar cell polarity regulator Vangl2

The planar cell polarity (PCP) pathway is a non-canonical Wnt signaling pathway, best known for controlling the collective polarization of cells. PCP is mediated by a set of core components including, among others, the transmembrane protein Vangl2. The current literature suggests a scaffolding function of Vangl2 in recruiting diverse partners for the establishment of intracellular complexes critical for PCP signaling. Yet, the molecular insights about Vangl2 function in these contexts is very limited due to the complete absence of mechanistic and structural studies. Here, we propose to fill this gap by integrating Vangl2 genetics, recent advances in our understanding of Vangl2 function, and AlphaFold2 predictions, in addressing pending questions related to PCP molecular mechanisms. We will capitalize on our strengths in biochemistry, biophysics, and structural biology to provide a holistic picture on the structures, the physical interactions, and the phospho-regulation of Vangl2. These findings will be instrumental in moving forward with the studies of the full-length membrane protein.