ArticleThe Journal of biological chemistry2010
Down-regulation of intestinal apical calcium entry channel TRPV6 by ubiquitin E3 ligase Nedd4-2.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Adaptor-mediated interaction between Kv1.3 and Nedd4-2 E3 ubiquitin ligase.Communications biology · 2026Article
- Selective TRPV2 Antagonists Derived from the Natural Product Piperlongumine Inhibit Cancer Cell Migration and Metastasis.ACS chemical biology · 2026Article
- Alterations in the microenvironment and the effects produced of TRPV5 in osteoporosis.Journal of translational medicine · 2023Review
- Nedd4-2 binding to 14-3-3 modulates the accessibility of its catalytic site and WW domains.Biophysical journal · 2022Article
- Calcium selective channel TRPV6: Structure, function, and implications in health and disease.Gene · 2022Review
- microRNA-454-mediated NEDD4-2/TrkA/cAMP axis in heart failure: Mechanisms and cardioprotective implications.Journal of cellular and molecular medicine · 2021Article
- Review
- Vitamin D and the intestine: Review and update.The Journal of steroid biochemistry and molecular biology · 2020Review
- Transgenic Expression of the Vitamin D Receptor Restricted to the Ileum, Cecum, and Colon of Vitamin D Receptor Knockout Mice Rescues Vitamin D Receptor-Dependent Rickets.Endocrinology · 2017Article
- PKC/Nedd4-2 Signaling Pathway Regulates the Cell Surface Expression of Drug Transporter hOAT1.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Expression of Cav1.3 calcium channel in the human and mouse colon: posttranscriptional inhibition by IFNγ.American journal of physiology. Gastrointestinal and liver physiology · 2017Article
- The role of Nedd4-1 WW domains in binding and regulating human organic anion transporter 1.American journal of physiology. Renal physiology · 2016Article
- Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.Physiological reviews · 2016Review
- Post-translational loss of renal TRPV5 calcium channel expression, Ca(2+) wasting, and bone loss in experimental colitis.Gastroenterology · 2013Article
- Uromodulin upregulates TRPV5 by impairing caveolin-mediated endocytosis.Kidney international · 2013Article
- Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation.FEBS letters · 2013Article
- Nedd4-2 does not regulate wt-CFTR in human airway epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2012Article
- Recent advances in our understanding of 1,25-dihydroxyvitamin D(3) regulation of intestinal calcium absorption.Archives of biochemistry and biophysics · 2012Review
- Suppression of intestinal calcium entry channel TRPV6 by OCRL, a lipid phosphatase associated with Lowe syndrome and Dent disease.American journal of physiology. Cell physiology · 2012Article
- Disease-causing mutations in the acidic motif of WNK4 impair the sensitivity of WNK4 kinase to calcium ions.Biochemical and biophysical research communications · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Nedd4-2 is an archetypal HECT ubiquitin E3 ligase that disposes target proteins for degradation. Because of the proven roles of Nedd4-2 in degradation of membrane proteins, such as epithelial Na(+) channel, we examined the effect of Nedd4-2 on the apical Ca(2+) channel TRPV6, which is involved in transcellular Ca(2+) transport in the intestine using the Xenopus laevis oocyte system. We demonstrated that a significant amount of Nedd4-2 protein was distributed to the absorptive epithelial cells in ileum, cecum, and colon along with TRPV6. When co-expressed in oocytes, Nedd4-2 and, to a lesser extent, Nedd4 down-regulated the protein abundance and Ca(2+) influx of TRPV6 and TRPV5, respectively. TRPV6 ubiquitination was increased, and its stability was decreased by Nedd4-2. The Nedd4-2 inhibitory effects on TRPV6 were partially blocked by proteasome inhibitor MG132 but not by the lysosome inhibitor chloroquine. The rate of TRPV6 internalization was not significantly altered by Nedd4-2. The HECT domain was essential to the inhibitory effect of Nedd4-2 on TRPV6 and to their association. The WW1 and WW2 domains interacted with TRPV6 terminal regions, and a disruption of the interactions by D204H and D376H mutations in the WW1 and WW2 domains increased TRPV6 ubiquitination and degradation. Thus, WW1 and WW2 may serve as a molecular switch to limit the ubiquitination of TRPV6 by the HECT domain. In conclusion, Nedd4-2 may regulate TRPV6 protein abundance in intestinal epithelia by controlling TRPV6 ubiquitination.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.