text: A majority of the adhesion GPCRs are orphan receptors and work is underway to de-orphanize many of these receptors.  Adhesion GPCRs get their name from their N-terminal domains that have adhesion-like domains, such as EGF, and the belief that they interact cell to cell and cell to extra cellular matrix. While ligands for many receptors are still not known, researchers are utilizing drug libraries to investigate compounds that can activate GPCRs and using these data for future ligand research.
  One adhesion GPCR, GPR56, has a known ligand, collagen III, which is involved in neural migration inhibition.  GPR56 has been shown to be the cause of polymicrogyria in humans and may play a role in cancer metastasis. The binding of collagen III to GPR56 occurs on the N-terminus and has been narrowed down to a short stretch of amino acids.  The N-terminus of GPR56 is naturally glycosylated, but this glycosylation is not necessary for collagen III binding. Collagen III, results in GPR56 to signal through Gα12/13 activating RhoA.