Regulation of pendrin by pH: dependence on glycosylation

Anie Azroyan , Kamel Laghmani , Gilles Crambert , David Mordasini , Alain Doucet , Aurélie Edwards (1)

1 UPMC - Université Pierre et Marie Curie - Paris 6

Mutations of the anion exchanger pendrin are responsible for Pendred syndrome, an autosomal recessive disease characterized by deafness and goiter. Pendrin is highly expressed in kidney collecting ducts, where it acts as a chloride/bicarbonate exchanger and thereby contributes to the regulation of acid-base homeostasis and blood pressure. This study aimed to characterize the intrinsic properties of pendrin. Mouse pendrin was transfected in HEK293 and OKP cells; its activity was determined by monitoring changes in intracellular pH induced by variations of trans-membrane anion gradients. Combining measu­re­ments of pendrin activity with mathe­matical modeling, we found that its affinities for Cl-, HCO3- and OH- vary with intracellular pH, resulting in increased activity at low intracellular pH. Pendrin maximal activity was also stimulated at low extra­cel­lular pH, sug­gesting the presence of intra- and extra-cellular proton regulatory sites. We identified 5 putative pendrin glyco­sylation sites, only two of which are used. Mutagenesis-induced disruption of pendrin glyco­sylation did not alter its cell surface expression, polarized targeting to the apical membrane and basal activity, but fully abrogated its sensitivity to extracellular pH. The hereto unknown regulation of pendrin by external pH may constitute a key mechanism in controlling ionic exchanges across the collecting duct and inner ear.

Mots clés: Life Sciences

Anie Azroyan, Kamel Laghmani, Gilles Crambert, David Mordasini, Alain Doucet, et al.. Regulation of pendrin by pH: dependence on glycosylation. Biochemical Journal, 2011, 434 (1), pp.61-72. ⟨10.1042/BJ20101411⟩. ⟨hal-00560691⟩