PT  - JOURNAL ARTICLE
AU  - Martin J. Lohse
AU  - Klaus Peter Hofmann
TI  - Spatial and Temporal Aspects of Signaling by G-Protein–Coupled Receptors
AID  - 10.1124/mol.115.100248
DP  - 2015 Sep 01
TA  - Molecular Pharmacology
PG  - 572--578
VI  - 88
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/88/3/572.short
4100  - http://molpharm.aspetjournals.org/content/88/3/572.full
SO  - Mol Pharmacol2015 Sep 01; 88
AB  - Signaling by G-protein–coupled receptors is often considered a uniform process, whereby a homogeneously activated proportion of randomly distributed receptors are activated under equilibrium conditions and produce homogeneous, steady-state intracellular signals. While this may be the case in some biologic systems, the example of rhodopsin with its strictly local single-quantum mode of function shows that homogeneity in space and time cannot be a general property of G-protein–coupled systems. Recent work has now revealed many other systems where such simplicity does not prevail. Instead, a plethora of mechanisms allows much more complex patterns of receptor activation and signaling: different mechanisms of protein-protein interaction; temporal changes under nonequilibrium conditions; localized receptor activation; and localized second messenger generation and degradation—all of which shape receptor-generated signals and permit the creation of multiple signal types. Here, we review the evidence for such pleiotropic receptor signaling in space and time.