ArticleThe Journal of biological chemistry2014
Unique regulation of human Na+/H+ exchanger 3 (NHE3) by Nedd4-2 ligase that differs from non-primate NHE3s.
Article in The Journal of biological chemistry, 2014. 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, 16 citations in OpenAlex.
- Regulation of the intestinal NaAmerican journal of physiology. Cell physiology · 2024Article
- SGK3 promotes vascular calcification via Pit-1 in chronic kidney disease.Theranostics · 2024Article
- Inhibition of protein kinase C-α and activation of ezrin byAmerican journal of physiology. Endocrinology and metabolism · 2023Article
- Review
- Metformin Inhibits NaFrontiers in physiology · 2022Article
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- Ubiquitin-specific peptidase 7 (USP7) and USP10 mediate deubiquitination of human NHE3 regulating its expression and activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Role of the Ubiquitin Proteasome System in the Regulation of Blood Pressure: A Review.International journal of molecular sciences · 2020Review
- Hyperglycemia promotes microvillus membrane expression of DMT1 in intestinal epithelial cells in a PKCα-dependent manner.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- The Ubiquitin Ligase Nedd4L Regulates the Na/K/2Cl Co-transporter NKCC1/SLC12A2 in the Colon.The Journal of biological chemistry · 2017Article
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Authors and funding
4 authors at 1 institution in 2 countries.
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Abstract
Na(+)/H(+) exchanger NHE3 expressed in the intestine and kidney plays a major role in NaCl and HCO3 (-) absorption that is closely linked to fluid absorption and blood pressure regulation. The Nedd4 family of E3 ubiquitin ligases interacts with a number of transporters and channels via PY motifs. A comparison of NHE3 sequences revealed the presence of PY motifs in NHE3s from human and several non-human primates but not in non-primate NHE3s. In this study we evaluated the differences between human and non-primate NHE3s in ubiquitination and interaction with Nedd4-2. We found that Nedd4-2 ubiquitinated human NHE3 (hNHE3) and altered its expression and activity. Surprisingly, rat NHE3 co-immunoprecipitated Nedd4-2, but its expression and activity were not altered by silencing of Nedd4-2. Ubiquitination by Nedd4-2 rendered hNHE3 to undergo internalization at a significantly greater rate than non-primate NHE3s without altering protein stability. Insertion of a PY motif in rabbit NHE3 recapitulated the interaction with Nedd4-2 and enhanced internalization. Thus, we propose a new model where disruption of Nedd4-2 interaction elevates hNHE3 expression and activity.
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