ArticleAmerican journal of physiology. Renal physiology2013
Activation of the cAMP/PKA pathway induces UT-A1 urea transporter monoubiquitination and targets it for lysosomal degradation.
Article in American journal of physiology. Renal physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Tissue Distribution, Expression and Regulation of Urea Transporters.Sub-cellular biochemistry · 2025Review
- E3 ligase MDM2 mediates urea transporter-A1 ubiquitination under either constitutive or stimulatory conditions.American journal of physiology. Renal physiology · 2019Article
- Ghrelin-Induced Sodium Reabsorption Is Mediated by PKA and Microtubule-DependentJournal of the Endocrine Society · 2019Article
- Adenine acts in the kidney as a signaling factor and causes salt- and water-losing nephropathy: early mechanism of adenine-induced renal injury.American journal of physiology. Renal physiology · 2019Article
- CaMolecular neurobiology · 2019Article
- Identification of UT-A1- and AQP2-interacting proteins in rat inner medullary collecting duct.American journal of physiology. Cell physiology · 2018Article
- Data integration in physiology using Bayes' rule and minimum Bayes' factors: deubiquitylating enzymes in the renal collecting duct.Physiological genomics · 2017Article
- Downregulation of urea transporter UT-A1 activity by 14-3-3 protein.American journal of physiology. Renal physiology · 2015Article
- Urea transporter proteins as targets for small-molecule diuretics.Nature reviews. Nephrology · 2015Review
- Ubiquitin-activating enzyme activity contributes to differential accumulation of mutant huntingtin in brain and peripheral tissues.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
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4 authors at 2 institutions in 2 countries.
Funding
Abstract
Regulation of urea transporter UT-A1 in the kidney is important for the urinary concentrating mechanism. We previously reported that activation of the cAMP/PKA pathway by forskolin (FSK) leads to UT-A1 ubiquitination, endocytosis, and degradation. In this study, we discovered that FSK-induced UT-A1 ubiquitination is monoubiquitination as judged by immunoblotting with specific ubiquitin antibodies to the different linkages of the ubiquitin chain. UT-A1 monoubiquitination induced by FSK was processed mainly on the cell plasma membrane. Monoubiquitination facilitates UT-A1 endocytosis, and internalized UT-A1 is accumulated in the early endosome. Inhibition of ubiquitination by E1 ubiquitin-activating enzyme inhibitor PYR-41 significantly reduced FSK-induced UT-A1 endocytosis and degradation. Interestingly, FSK-stimulated UT-A1 degradation occurs through a lysosomal protein degradation system. We further found that the PKA phosphorylation sites of UT-A1 at Ser486 and Ser499 are required for FSK-induced UT-A1 monoubiquitination. The physiological significance was confirmed using rat kidney inner medullary collecting duct suspensions, which showed that vasopressin treatment promotes UT-A1 ubiquitination. We conclude that unlike under basal conditions in which UT-A1 is subject to polyubiquitination and proteasome-mediated protein degradation, activation of UT-A1 by FSK induces UT-A1 monoubiquitination and protein lysosomal degradation.
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