GPCRs serve as crucial mediators for various cellular signal transduction events that provide the means for cells, tissues, organs and whole organisms to react properly to changing environmental requirements. Their functions are extremely diverse as they regulate many physiological processes related to neurological and neurodegenerative functions, cardiovascular mechanisms, and metabolic control.1 GPCRs can also act as co-receptors for cellular entry of the human immune deficiency virus (HIV).2

Extracellular signaling is triggered through hormones, neurotransmitters, chemokines, calcium ions, light, and odorants and leads to the activation of GPCRs, resulting in a cascade of signaling through various cellular pathways.3 The GPCR designation relates to the intracellular signaling through guanine nucleotide-binding proteins (G proteins) although alternative mechanisms have been described recently.4

The estimated number of GPCRs in the human genome is 800. A large number belong to the subfamily of odorant receptors. Due to their many essential physiological functions, GPCRs play an important role in drug discovery. More than 60% of the current drug targets are focused on GPCRs and a quarter of the 200 top selling drugs are based on GPCRs.5 The various indications and the more detailed mechanisms of drug and GPCR interactions are described in subsequent chapters.

Common to all GPCRs is their topology of seven transmembrane-spanning domains (7TMs) consisting of a-helical structures and they are therefore also called 7TM receptors. Each GPCR possesses an extracellular N-terminus and an intracellular C-terminus with various intracellular and extracellular loop regions connecting the transmembrane regions. This chapter will describe the different families of GPCRs, their functions, and their couplings to G proteins. Alternative signaling mechanisms for GPCRs are also discussed. Finally, the cellular trafficking of GPCRs is described.

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