Receptor Adaptation Mechanisms


Receptor adaptation mechanisms involve regulation of the number, sensitivity and subcellular localization of receptors that detect environmental cues and convert extracellular signals into a change of intracellular events.

Keywords: regulation of receptor desensitization; downregulation and gene expression; pharmacology; G protein‐coupled receptors; β‐adrenergic receptor; rhodopsin; G protein‐coupled receptor kinase; arrestins; nicotinic acetylcholine receptor

Figure 1.

Schematic representation of intracellular events leading to homologous and heterologous desensitization following activation of β‐adrenergic receptor (β‐AR). β‐AR couples to Gs leading to activation of AC. Agonist activated β‐AR is phosphorylated by β‐ARK at its C‐terminus. Phosphorylated β‐AR interacts with β‐arrestin that prevents Gs activation by the receptor (homologous desensitization). β‐arrestin also acts as an adaptor protein to facilitate β‐AR internalization and to engage β‐AR to MAP kinase (MAPK) pathway. In heterologous desensitization, β‐AR is phosphorylated by protein kinases other than β‐ARK. For example PKA, which is activated by cAMP can modify β‐AR leading to diminished receptor activity towards Gs. Phosphorylated serine/threonine residues in β‐AR are labelled as orange dots.

Figure 2.

Rhodopsin mediates visual transduction in the rod outer segments (ROS). ROS are specialized compartments consisting of 2000 discs which are invaginated plasma membranes (lower panel). Shown in the upper panel is a section of ROS depicting signalling proteins and their distribution in disc or plasma membranes. Light activates rhodopsin by triggering isomerization of 11‐cis retinal to become all‐trans retinal in rhodopsin. Activated rhodopsin interacts with transducin (Gt), which turns on a cGMPphosphodiesterase (PDE). PDE catalyses the hydrolysis of cGMP leading to a reduced level of cGMP. Cyclic GMP is generated by guanylate cyclase (GC) and is responsible for opening of cGMP channels in the plasma membrane. Light leads to hyperpolarization of photoreceptors due to breakdown of cGMP resulting in closure of cGMP channels.To terminate the activity of activated rhodopsins, rhodopsin kinase modifies rhodopsins by phosphorylation. Phosphorylated rhodopsin interacts with arrestin that prevents its activity to activate Gt. Stable rhodopsin/arrestin complexes may be internalized for degradation of rhodopsins and to initiate apoptosis of photoreceptors.



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Further Reading

Duclert A and Changeux JP (1995) Acetylcholine receptor gene expression at the developing neuromuscular junction. Physiological Reviews 75: 339–368.

Krupnick JG and Benovic JL (1998) The role of receptor kinases and arrestins in G protein‐coupled receptor regulation. Annual Review of Pharmacology and Toxicology 38: 289–319.

Luttrell LM and Lefkowitz RL (2002) The role of β‐arrestins in the termination and transduction of G‐protein‐coupled receptor signals. Journal of Cell Science 115: 455–465.

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How to Cite close
Shieh, Bih‐Hwa(Jan 2006) Receptor Adaptation Mechanisms. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0004077]