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Protein kinase A regulates chloride conductance in endocytic vesicles from proximal tubule

Abstract

REGULATION of ion transport by phosphorylation and G proteins occurs in several epithelial and non-epithelial cell plasma membranes1–5. It is not known whether transporters on intracellular membranes are target sites for second messengers. Here we present direct evidence that a chloride conductance in endocytic vesicles from rabbit proximal tubule is activated by phosphorylation through a cyclic AMP-dependent protein kinase. To measure chloride transport, endocytic vesicles were labelled in vivo with a Cl−-sensitive fluorescent indicator6–8. It was found that labelled endosomes contained an inward proton pump and a chloride conductance, but no ion-coupled chloride transport, and that the chloride conductance was regulated by protein kinase A. These results, taken together with measurements of chloride effects on ATP-dependent acidification, suggest that endosomal pH can be controlled by phosphorylation of a stilbene-sensitive conductive chloride transporter.

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Bae, HR., Verkman, A. Protein kinase A regulates chloride conductance in endocytic vesicles from proximal tubule. Nature 348, 637–639 (1990). https://doi.org/10.1038/348637a0

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