Regulation of pendrin by pH: dependence on glycosylation

Azroyan, Anie; Laghmani, Kamel; Crambert, Gilles; Mordasini, David; Doucet, Alain; Edwards, Aurélie

doi:10.1042/bj20101411

Cited by 34 publications

(35 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are conflicting reports about whether or not these two sites are actually glycosylated in prestin (Matsuda et al, 2004;Navaratnam et al, 2005;Rajagopalan et al, 2010). Cell surface expression is unaffected by substitution of both asparagines with alanine residues, and these mutant proteins exhibited only minor alterations in their physiological properties (Matsuda et al, 2004;Navaratnam et al, 2005;Rajagopalan et al, 2010;Azroyan et al, 2011). However, recent evidence demonstrated that the mouse Slc26A4 paralog, pendrin, is glycosylated at the equivalent sites (N167 and N172) (Azroyan et al, 2011).…”

Section: Discussionmentioning

confidence: 97%

“…Cell surface expression is unaffected by substitution of both asparagines with alanine residues, and these mutant proteins exhibited only minor alterations in their physiological properties (Matsuda et al, 2004;Navaratnam et al, 2005;Rajagopalan et al, 2010;Azroyan et al, 2011). However, recent evidence demonstrated that the mouse Slc26A4 paralog, pendrin, is glycosylated at the equivalent sites (N167 and N172) (Azroyan et al, 2011). Undoubtedly, these models are inadequate to explain the contribution of the MESH motif to the conformational changes of prestrin from the compact to expanded state, with membrane potential determining the probability of each conformation (Oliver et al, 2001;Dallos and Fakler, 2002).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A motif of eleven amino acids is a structural adaptation that facilitates motor capability of eutherian prestin

Tan

Pecka

Tang

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

SummaryCochlear outer hair cells (OHCs) alter their length in response to transmembrane voltage changes. This so-called electromotility is the result of conformational changes of membrane-bound prestin. Prestin-based OHC motility is thought to be responsible for cochlear amplification, which contributes to the exquisite frequency selectivity and sensitivity of mammalian hearing. Prestin belongs to an anion transporter family, the solute carrier protein 26A (SLC26A). Prestin is unique in this family in that it functions as a voltage-dependent motor protein manifested by two hallmarks, nonlinear capacitance and motility. Evidence suggests that prestin orthologs from zebrafish and chicken are anion exchangers or transporters with no motor function. We identified a segment of 11 amino acid residues in eutherian prestin that is extremely conserved among eutherian species but highly variable among non-mammalian orthologs and SLC26A paralogs. To determine whether this sequence represents a motif that facilitates motor function in eutherian prestin, we utilized a chimeric approach by swapping corresponding residues from the zebrafish and chicken with those of gerbil. Motility and nonlinear capacitance were measured from chimeric prestin-transfected human embryonic kidney 293 cells using a voltage-clamp technique and photodiode-based displacement measurement system. We observed a gain of motor function with both of the hallmarks in the chimeric prestin without loss of transport function. Our results show, for the first time, that the substitution of a span of 11 amino acid residues confers the electrogenic anion transporters of zebrafish and chicken prestins with motor-like function. Thus, this motif represents the structural adaptation that assists gain of motor function in eutherian prestin.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

A motif of eleven amino acids is a structural adaptation that facilitates motor capability of eutherian prestin

Tan

Pecka

Tang

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Pendrin has been found to have a relatively high affinity to external chloride also at high pH value, which can be important to allow bicarbonate secretion in state of alkalosis [54]. Pendrin activity is also regulated by external pH.…”

Section: Discussionmentioning

confidence: 99%

“…The effect of external pH is possibly related to allosteric modifications and represents an intrinsic pH effect. In vitro experiments in HEK cells demonstrated that sensitivity of pendrin to external pH depends on its glycosylation state [54]. Specifically, a low external pH stimulates pendrin activity.…”

Section: Discussionmentioning

confidence: 99%

Co-Regulated Pendrin and Aquaporin 5 Expression and Trafficking in Type-B Intercalated Cells under Potassium Depletion

Procino

Milano

Tamma

et al. 2013

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: We recently reported that aquaporin 5 (AQP5), a water channel never identified in the kidney before, co-localizes with pendrin at the apical membrane of type-B intercalated cells in the kidney cortex. Since co-expression of AQP5 and pendrin in the apical membrane domain is a common feature of several other epithelia such as cochlear and bronchial epithelial cells, we evaluated here whether this strict membrane association may reflect a co-regulation of the two proteins. To investigate this possibility, we analyzed AQP5 and pendrin expression and trafficking in mice under chronic K⁺ depletion, a condition that results in an increased ability of renal tubule to reabsorb bicarbonate, often leads to metabolic alkalosis and is known to strongly reduce pendrin expression. Methods: Mice were housed in metabolic cages and pair-fed with either a standard laboratory chow or a K⁺-deficient diet. AQP5 abundance was assessed by western blot in whole kidney homogenates and AQP5 and pendrin were localized by confocal microscopy in kidney sections from those mice. In addition, the short-term effect of changes in external pH on pendrin trafficking was evaluated by fluorescence resonance energy transfer (FRET) in MDCK cells, and the functional activity of pendrin was tested in the presence and absence of AQP5 in HEK 293 Phoenix cells. Results: Chronic K⁺ depletion caused a strong reduction in pendrin and AQP5 expression. Moreover, both proteins shifted from the apical cell membrane to an intracellular compartment. An acute pH shift from 7.4 to 7.0 caused pendrin internalization from the plasma membrane. Conversely, a pH shift from 7.4 to 7.8 caused a significant increase in the cell surface expression of pendrin. Finally, pendrin ion transport activity was not affected by co-expression with AQP5. Conclusions: The co-regulation of pendrin and AQP5 membrane expression under chronic K⁺-deficiency indicates that these two molecules could cooperate as an osmosensor to rapidly detect and respond to alterations in luminal fluid osmolality.

show abstract

“…Nitric oxide also contributes to intercalated cell transport protein regulation as it reduces pendrin protein abundance in the kidney without modulating pendrin subcellular localization in a cAMP-dependent manner (103). The regulation of pendrin also involves glycosylation-dependent processes (104,105). In addition to the regulation of acid-base status, it appears that pendrin expressed in kidney intercalated cells plays a role in controlling iodide homeostasis as well, especially during high water intake (106).…”

Section: Type B Intercalated Cells and Their Transport Processesmentioning

confidence: 99%

Collecting Duct Intercalated Cell Function and Regulation

Roy¹,

Al‐bataineh²,

Pastor-Soler

2015

Clinical Journal of the American Society of Nephrology

204

213

View full text Add to dashboard Cite

Intercalated cells are kidney tubule epithelial cells with important roles in the regulation of acid-base homeostasis. However, in recent years the understanding of the function of the intercalated cell has become greatly enhanced and has shaped a new model for how the distal segments of the kidney tubule integrate salt and water reabsorption, potassium homeostasis, and acid-base status. These cells appear in the late distal convoluted tubule or in the connecting segment, depending on the species. They are most abundant in the collecting duct, where they can be detected all the way from the cortex to the initial part of the inner medulla. Intercalated cells are interspersed among the more numerous segment-specific principal cells. There are three types of intercalated cells, each having distinct structures and expressing different ensembles of transport proteins that translate into very different functions in the processing of the urine. This review includes recent findings on how intercalated cells regulate their intracellular milieu and contribute to acid-base regulation and sodium, chloride, and potassium homeostasis, thus highlighting their potential role as targets for the treatment of hypertension. Their novel regulation by paracrine signals in the collecting duct is also discussed. Finally, this article addresses their role as part of the innate immune system of the kidney tubule.

show abstract

Regulation of pendrin by pH: dependence on glycosylation

Cited by 34 publications

References 46 publications

A motif of eleven amino acids is a structural adaptation that facilitates motor capability of eutherian prestin

A motif of eleven amino acids is a structural adaptation that facilitates motor capability of eutherian prestin

Co-Regulated Pendrin and Aquaporin 5 Expression and Trafficking in Type-B Intercalated Cells under Potassium Depletion

Collecting Duct Intercalated Cell Function and Regulation

Contact Info

Product

Resources

About