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Published on: September 1, 2015
"ADPKD-omics": determinants of cyclic AMP levels in renal epithelial cells
Yash R Mehta1, Spencer A Lewis1, Kirby T Leo1
1Epithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Abstract:
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.
Insights
Cyclic adenosine monophosphate (cAMP) regulation in kidney cells impacts water balance and autosomal dominant polycystic kidney disease (ADPKD). This study identifies key proteins controlling cAMP levels in kidney tubules, aiding ADPKD research.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- Cyclic adenosine monophosphate (cAMP) signaling is crucial for kidney function.
- Dysregulation of cAMP is implicated in water balance disorders and autosomal dominant polycystic kidney disease (ADPKD).
Purpose of the Study:
- To identify and characterize proteins that regulate cAMP levels in kidney epithelial cells.
- To determine the expression of these cAMP-regulating proteins across kidney tubule segments.
- To provide a resource for understanding ADPKD pathogenesis.
Main Methods:
- Review of genes encoding cAMP level determinants.
- Analysis of RNA-sequencing and protein mass spectrometry data for 14 kidney tubule segments.
- Integration of "autosomal dominant polycystic kidney disease-omics" data.
Main Results:
- A comprehensive list of cAMP-level determinants, including G protein-coupled receptors, adenylyl cyclases, and phosphodiesterases, was compiled.
- Expression patterns of these proteins across kidney tubule segments were identified.
- A specialized database of the primary cilium proteome was created.
Conclusions:
- This curated list of proteins provides a valuable resource for understanding cAMP regulation in kidney epithelial cells.
- Identifying these determinants may offer insights into the progression of autosomal dominant polycystic kidney disease.
- Compartmentalized cAMP signaling in primary cilia is highlighted as an area for further investigation.
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