Adhesion GPCR-Related Protein Networks

Adhesion G protein-coupled receptors (aGPCRs/ADGRs) are unique receptors that combine cell adhesion and signaling functions. Protein networks related to ADGRs exert diverse functions, e.g., in tissue polarity, cell migration, nerve cell function, or immune response, and are regulated via different mechanisms. The large extracellular domain of ADGRs is capable of mediating cell-cell or cell-matrix protein interactions. Their intracellular surface and domains are coupled to downstream signaling pathways and often bind to scaffold proteins, organizing membrane-associated protein complexes. The cohesive interplay between ADGR-related network components is essential to prevent severe disease-causing damage in numerous cell types. Consequently, in recent years, attention has focused on the decipherment of the precise molecular composition of ADGR protein complexes and interactomes in various cellular modules. In this chapter, we discuss the affiliation of ADGR networks to cellular modules and how they can be regulated, pinpointing common features in the networks related to the diverse ADGRs. Detailed decipherment of the composition of protein networks should provide novel targets for the development of novel therapies with the aim to cure human diseases related to ADGRs.