GPCR‐omics of the Nephron: Mapping Receptors Along the Renal Tubule

Kidney transport and other renal functions are regulated by multiple G‐protein coupled receptors (GPCRs) expressed along the renal tubule. Development of unbiased ‘‐omics’ approaches and next‐generation sequencing (NGS)‐based techniques, including transcriptomics in microdissected renal tubules, single‐cell transcriptomics, and proteomics in microdissected tubules have provided a means of identifying patterns of GPCR expression. To allow for complete GPCR mapping, we first curated a comprehensive list of GPCRs in the genomes of rats, mice and humans ( https://hpcwebapps.cit.nih.gov/ESBL/Database/GPCRs/ ). From this database we mapped the expression of 758 GPCRs across fourteen nephron segments using existing transcriptomic data, providing a complete picture of GPCR expression ( https://hpcwebapps.cit.nih.gov/ESBL/Database/GPCRs/TubuleTPM.html ). We used this list to mine segment‐specific and cell‐type specific expression data from RNA‐seq studies to identify GPCRs that are selectively expressed in discrete tubule segments. Each GPCR found to be selectively expressed was also matched to known ligands, coupled G‐proteins and known physiological roles in the segment in which it is selectively expressed. Comparisons of these mapped GPCRs with other transcriptomics and proteomics datasets, functional data from isolated perfused tubules, and micro‐puncture studies in the literature confirms patterns of expression for well‐known receptors and identifies lesser known GPCRs that are likely to play key roles in regulation of renal tubule transport and function. This study provides data resources for GPCR expression across the renal tubule, highlighting both well‐known GPCRs and understudied receptors in order to provide guidance for future experiments.