Progress in demystification of adhesion G protein-coupled receptors

Adhesion G protein-coupled receptors (aGPCR) form the second largest class of GPCR. They are phylogenetically old and have been highly conserved during evolution. Mutations in representatives of this class are associated with severe diseases such as Usher Syndrome, a combined congenital deaf-blindness, or bifrontal parietal polymicrogyria. The main characteristics of aGPCR are their enormous size and the complexity of their N termini. They contain a highly conserved GPCR proteolytic site (GPS) and several functional domains that have been implicated in cell-cell and cell-matrix interactions. Adhesion GPCR have been proposed to serve a dual function as adhesion molecules and as classical receptors. However, until recently there was no proof that aGPCR indeed couple to G proteins or even function as classical receptors. In this review, we have summarized and discussed recent evidence that aGPCR present many functional features of classical GPCR, including multiple G protein-coupling abilities, G protein-independent signaling and oligomerization, but also specific signaling properties only found in aGPCR.