Epithelial Systems Biology Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Am J Physiol Renal Physiol. 2021 Jul 1;321(1):F50-F68. doi: 10.1152/ajprenal.00077.2021. Epub 2021 May 24.
Kidney transport and other renal functions are regulated by multiple G protein-coupled receptors (GPCRs) expressed along the renal tubule. The rapid, recent appearance of comprehensive unbiased gene expression data in the various renal tubule segments, chiefly RNA sequencing and protein mass spectrometry data, has provided a means of identifying patterns of GPCR expression along the renal tubule. To allow for comprehensive mapping, we first curated a comprehensive list of GPCRs in the genomes of mice, rats, and humans (https://hpcwebapps.cit.nih.gov/ESBL/Database/GPCRs/) using multiple online data sources. We used this list to mine segment-specific and cell type-specific expression data from RNA-sequencing studies in microdissected mouse tubule segments to identify GPCRs that are selectively expressed in discrete tubule segments. Comparisons of these mapped mouse GPCRs with other omics datasets as well as functional data from isolated perfused tubule and micropuncture studies confirmed patterns of expression for well-known receptors and identified poorly studied GPCRs that are likely to play roles in the regulation of renal tubule function. Thus, we provide data resources for GPCR expression across the renal tubule, highlighting both well-known GPCRs and understudied receptors to provide guidance for future studies.
肾脏转运和其他肾脏功能受沿肾小管表达的多种 G 蛋白偶联受体 (GPCR) 调节。最近,各种肾小管段的全面、无偏基因表达数据(主要是 RNA 测序和蛋白质质谱数据)的快速出现,为识别沿肾小管 GPCR 表达模式提供了一种手段。为了进行全面映射,我们首先使用多个在线数据源,在小鼠、大鼠和人类的基因组中(https://hpcwebapps.cit.nih.gov/ESBL/Database/GPCRs/)编纂了 GPCR 的综合清单。我们使用该列表从微切割的小鼠肾小管段的 RNA 测序研究中挖掘特定节段和特定细胞类型的表达数据,以识别在离散肾小管段中选择性表达的 GPCR。将这些映射的小鼠 GPCR 与其他组学数据集以及分离灌注小管和微穿刺研究的功能数据进行比较,证实了已知受体的表达模式,并确定了研究较少的 GPCR,这些 GPCR 可能在调节肾脏小管功能中发挥作用。因此,我们提供了跨肾脏小管的 GPCR 表达数据资源,突出了众所周知的 GPCR 和研究较少的受体,为未来的研究提供指导。