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RASSLing with receptors

Nature Biotechnology volume 17, pages 131–132 (1999)Cite this article

The human genome is thought to encode over a thousand G–protein coupled receptors (GPCRs). One of the more daunting tasks in the postgenomic era will be defining true physiological roles for these molecules and the pathways they initiate. Approaches that allow a specific receptor to be activated at will in whole animals will be invaluable. In this issue, Bruce Conklin and colleagues1 describe an in vivo validation of their protein engineering solution to this problem—an approach likely to be broadly useful for dissecting GPCR function, providing models for GPCR–linked diseases, and perhaps even controlling GPCRs for therapeutic purposes.

GPCRs are seven–transmembrane domain proteins that transduce extracellular signals, as diverse as photons or peptide hormones, into a wide range of physiological events—from hormone secretion to alterations in heart rate. Extracellular stimuli cause conformational changes in the receptor, which then activates the associated heterotrimeric G protein inside the cell. The ensuing cellular events depend on both the type of G protein (there are four main ones) and the type of cell. For example, the activation of Gi–coupled receptors reduces intracellular cAMP levels, slowing myocyte contraction in the heart or altering neurotransmitter release in the brain.

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Figure 1: Getting specific: Gi–coupled signaling of the κ;–opioid receptor can be activated by natural neuropeptides such as dynorphin, or synthetic agonists such as spiradoline.

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  1. a staff scientist at ARIAD Pharmaceuticals Inc., 26 Landsdowne Street, Cambridge, 02139, MA

    Tim Clackson

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  1. Tim Clackson
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Clackson, T. RASSLing with receptors. Nat Biotechnol 17, 131–132 (1999). https://doi.org/10.1038/6128

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