Seven transmembrane receptors: something old, something new

• Published in: Acta Physiologica 2007-05, Vol.190 (1), p.9-19
• Main Author: Lefkowitz, R.J
• Format: Article
• Language: English
• Subjects: adenylate cyclase; Animals; Arrestins - physiology; Biological and medical sciences; cell signalling; desensitization; DNA, Complementary - genetics; Fundamental and applied biological sciences. Psychology; G-Protein-Coupled Receptor Kinases - physiology; GPCR; Humans; Mutation - genetics; receptor; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - physiology; Signal Transduction - physiology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; β-arrestin
• ISSN: 1748-1716; 1748-1708; 1748-1716
• DOI: 10.1111/j.1365-201X.2007.01693.x

Receptors for hormones, neurotransmitters, drugs, sensory stimuli and many other agents represent the gateway to cellular metabolism and activity. They regulate virtually all physiological processes in mammals. Yet as recently as 40 years ago their very existence was still in question. One class of receptors, those coupled to G proteins (also known as GPCRs or seven transmembrane receptors) comprise by far the largest group (approx. 1000), and are the most important target of clinically used drugs. Here I provide a very personal retrospective of research over the past 35 years which ultimately led to the identification, purification, reconstitution and cloning of the adrenergic receptors; the discovery of their homology with the seven transmembrane spanning visual light receptor rhodopsin and the realization that there was a large gene family of G protein coupled receptors; the elucidation of the molecular mechanisms of receptor desensitization and signalling through G protein-coupled receptor kinases and β-arrestins; and the appreciation that the structure, signalling, and regulatory mechanisms of the receptors are all highly conserved across the large receptor superfamily.