ArticleThe Journal of biological chemistry2008
Phosphorylation and ankyrin-G binding of the C-terminal domain regulate targeting and function of the ammonium transporter RhBG.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Discovery of a potential novel pharmacogenomic biomarker on ANK3 gene for liafensine, a triple reuptake inhibitor for treatment-resistant depression.Translational psychiatry · 2026Trial
- Rhbg interaction with CA-IV and its effects on NHAmerican journal of physiology. Cell physiology · 2025Article
- Chloride Gradient Is Involved in Ammonium Influx in Human Erythrocytes.International journal of molecular sciences · 2024Article
- Pleiotropic Ankyrins: Scaffolds for Ion Channels and Transporters.Channels (Austin, Tex.) · 2022Review
- Roles and mechanisms of ankyrin-G in neuropsychiatric disorders.Experimental & molecular medicine · 2022Review
- The ammonia transporter RhCG modulates urinary acidification by interacting with the vacuolar proton-ATPases in renal intercalated cells.Kidney international · 2018Article
- Ammonia Transporters and Their Role in Acid-Base Balance.Physiological reviews · 2017Review
- Isoforms of Spectrin and Ankyrin Reflect the Functional Topography of the Mouse Kidney.PloS one · 2016Article
- Evidence of a structural and functional ammonium transporter RhBG·anion exchanger 1·ankyrin-G complex in kidney epithelial cells.The Journal of biological chemistry · 2015Article
- Ammonia transport in the kidney by Rhesus glycoproteins.American journal of physiology. Renal physiology · 2014Review
- Expression of the ammonia transporter family member, Rh B Glycoprotein, in the human kidney.American journal of physiology. Renal physiology · 2013Article
- Renal ammonia excretion in response to hypokalemia: effect of collecting duct-specific Rh C glycoprotein deletion.American journal of physiology. Renal physiology · 2013Article
- Intercalated cell-specific Rh B glycoprotein deletion diminishes renal ammonia excretion response to hypokalemia.American journal of physiology. Renal physiology · 2013Article
- Molecular physiology of the Rh ammonia transport proteins.Current opinion in nephrology and hypertension · 2010Review
- Membrane domains based on ankyrin and spectrin associated with cell-cell interactions.Cold Spring Harbor perspectives in biology · 2009Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RhBG, a human member of the Amt/Mep/Rh/superfamily of ammonium transporters, has been shown to facilitate NH(3) transport and to be anchored to the basolateral plasma membrane of kidney epithelial cells, via ankyrin-G. We showed here that triple alanine substitution of the (419)FLD(421) sequence, which links the cytoplasmic C-terminal domain of RhBG to ankyrin-G, not only disrupted the interaction of RhBG with the spectrin-based skeleton but also delayed its cell surface expression, decreased its plasma membrane stability, and abolished its NH(3) transport function in epithelial cell lines. Similarly, we demonstrated that both anchoring to the membrane skeleton and ammonium transport activity are regulated by the phosphorylation status of the C-terminal tail of RhBG. Tyrosine 429, which belongs to the previously reported YED basolateral targeting signal of RhBG, was demonstrated to be phosphorylated in vitro using purified Src and Syk kinases and ex vivo by analyzing the effect of pervanadate treatment on wild-type RhBG or Y429A mutants. Then, we showed that Y429D and Y429E mutations, mimicking constitutive phosphorylation, abolished NH(3) transport and enhanced Triton X-100 solubilization of RhBG from the cell membrane. In contrast, the nonphosphorylated/nonphosphorylatable Y429A and Y429F mutants behaved the same as wild-type RhBG. Conversely, Y/A or Y/F but not Y/E or Y/D mutations of residue 429 abolished the exclusive basolateral localization of RhBG in polarized epithelial cells. All these results led to a model in which targeting and ammonium transport function of RhBG are regulated by both phosphorylation and membrane skeleton binding of the C-terminal cytoplasmic domain.
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