Combinatorial expression of GPCR isoforms affects signalling and drug responses.

ABSTRACT: G-protein-coupled receptors (GPCRs) are membrane proteins that modulate physiology across human tissues in response to extracellular signals. GPCR-mediated signalling can differ because of changes in the sequence^1,2 or expression³ of the receptors, leading to signalling bias when comparing diverse physiological systems⁴. An underexplored source of such bias is the generation of functionally diverse GPCR isoforms with different patterns of expression across different tissues. Here we integrate data from human tissue-level transcriptomes, GPCR sequences and structures, proteomics, single-cell transcriptomics, population-wide genetic association studies and pharmacological experiments. We show how a single GPCR gene can diversify into several isoforms with dis

SUBMITTER: Marti-Solano M 

PROVIDER: S-EPMC7611127 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature