AI Article Synopsis
- GPCRs are a large family of receptors that communicate signals through G proteins and β-arrestins, often leading to "biased" signaling where different pathways are activated to different extents.
- One factor affecting this biased signaling is "location bias," which means that the receptor's cellular location can influence the type of signaling pathways activated.
- The review examines how GPCRs are located and function in various parts of the cell, the implications of this for drug interactions, and how understanding location bias could lead to better therapies targeting GPCRs.
Article Abstract
G protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors and primarily signal through two main effector proteins: G proteins and β-arrestins. Many agonists of GPCRs promote "biased" responses, in which different cellular signaling pathways are activated with varying efficacies. The mechanisms underlying biased signaling have not been fully elucidated, with many potential "hidden variables" that regulate this behavior. One contributor is "location bias," which refers to the generation of unique signaling cascades from a given GPCR depending upon the cellular location at which the receptor is signaling. Here, we review evidence that GPCRs are expressed at and traffic to various subcellular locations and discuss how location bias can impact the pharmacologic properties and characterization of GPCR agonists. We also evaluate how differences in subcellular environments can modulate GPCR signaling, highlight the physiological significance of subcellular GPCR signaling, and discuss the therapeutic potential of exploiting GPCR location bias.
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| http://dx.doi.org/10.1002/bies.202300123 | DOI Listing |
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