Epithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Epithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Kidney Int. 2022 Jan;101(1):47-62. doi: 10.1016/j.kint.2021.10.014. Epub 2021 Oct 29.
The regulation of cyclic adenosine monophosphate (cAMP) levels in kidney epithelial cells is important in at least 2 groups of disorders, namely water balance disorders and autosomal dominant polycystic kidney disease. Focusing on the latter, we review genes that code for proteins that are determinants of cAMP levels in cells. We identify which of these determinants are expressed in the 14 kidney tubule segments using recently published RNA-sequencing and protein mass spectrometry data ("autosomal dominant polycystic kidney disease-omics"). This includes G protein-coupled receptors, adenylyl cyclases, cyclic nucleotide phosphodiesterases, cAMP transporters, cAMP-binding proteins, regulator of G protein-signaling proteins, G protein-coupled receptor kinases, arrestins, calcium transporters, and calcium-binding proteins. In addition, compartmentalized cAMP signaling in the primary cilium is discussed, and a specialized database of the proteome of the primary cilium of cultured "IMCD3" cells is provided as an online resource (https://esbl.nhlbi.nih.gov/Databases/CiliumProteome/). Overall, this article provides a general resource in the form of a curated list of proteins likely to play roles in determination of cAMP levels in kidney epithelial cells and, therefore, likely to be determinants of progression of autosomal dominant polycystic kidney disease.
细胞内环磷酸腺苷(cAMP)水平的调节在至少 2 组疾病中很重要,即水平衡紊乱和常染色体显性多囊肾病。本文聚焦于后者,我们综述了编码细胞中 cAMP 水平决定因子的蛋白的基因。我们利用最近发表的 RNA 测序和蛋白质质谱数据(“常染色体显性多囊肾病组学”),确定了这些决定因子在 14 个肾小管段中的哪些部分表达。这包括 G 蛋白偶联受体、腺苷酸环化酶、环核苷酸磷酸二酯酶、cAMP 转运蛋白、cAMP 结合蛋白、G 蛋白信号调节蛋白、G 蛋白偶联受体激酶、抑制蛋白、钙转运蛋白和钙结合蛋白。此外,还讨论了初级纤毛中的局域化 cAMP 信号转导,并提供了一个在线资源(https://esbl.nhlbi.nih.gov/Databases/CiliumProteome/),用于培养的“IMCD3”细胞的初级纤毛蛋白质组的专门数据库。总的来说,本文提供了一个经过整理的蛋白质列表,这些蛋白质可能在决定肾脏上皮细胞中 cAMP 水平方面发挥作用,因此可能是常染色体显性多囊肾病进展的决定因素。