Proteomic Approaches to Investigate Regulated Trafficking and Signaling of G Protein–Coupled Receptors

Advances in proteomic methodologies based on quantitative mass spectrometry are now transforming pharmacology and experimental biology more broadly. The present review will discuss several examples based on work in the author’s laboratory, which focuses on delineating relationships between G protein–coupled receptor signaling and trafficking in the endocytic network. The examples highlighted correspond to those discussed in a talk presented at the 2019 EB/ASPET meeting, which was organized by Professor Joe Beavo to commemorate his receipt of the Julius Axelrod Award. SIGNIFICANCE STATEMENT GPCRs are allosteric machines that signal by interacting with other cellular proteins, and this, in turn, is determined by a complex interplay between the biochemical, subcellular localization, and membrane trafficking properties of receptors relative to transducer and regulatory proteins. The present minireview highlights recent advances and challenges in elucidating this dynamic cell biology and toward delineating the cellular basis of drug action at the level of defined GPCR interaction networks using proteomic approaches enabled by quantitative mass spectrometry.