Heptahelical Receptor Signaling: Beyond the G Protein Paradigm

Heptahelical receptors, so called because of their conserved structure featuring seven α-helical transmembrane spans, mediate physiological responses to a remarkably diverse array of stimuli. These include hormones, neurotransmitters, small peptides, proteins, lipids and ions, as well as sensory stimuli such as odorants, pheromones, bitter and sweet tastants, and photons. This superfamily of receptors contains >1,000 members, making it the largest class of cell surface molecules in the mammalian genome. Moreover, it was found recently that heptahelical receptors account for >5% of the total genes in the Caenorhabditus elegans genome (Bargmann, 1998), testifying to the importance of this family and demonstrating that the structure of these receptors has been highly conserved throughout evolution. For many years, this family of receptors has been referred to as G protein– coupled, a term based on the well documented paradigm that such receptors interact with and signal through heterotrimeric G proteins....