Work

The Multifunctional Exchangers SLC26A7 and SLC26A9 Are Also Sodium-Dependent Transporters of Inorganic Phosphate

Year: 2026

Type: article

Abstract: Background: The regulation of inorganic phosphate (Pi) homeostasis is predominantly mediated by the Pi transporters belonging to the SLC34 and SLC20 families of solute carriers. However, not all Pi handling can be explained by these transporters. In this study, we sought to identify novel Pi transporters in accordance with prior findings on inhibition patterns. Methods: We have performed a functional screening of new Pi carriers using the Xenopus laevis oocyte expression system, focusing on the SLC26 family, and corroboration in cell culture. Results: Both SLC26A7 and SLC26A9 have been shown to express sodium-activated Pi uptakes with approximately 200 µmol/L Pi affinity. In both cases, Pi transport is inhibited by increasing pH and by phosphonoformate, arsenate, bicarbonate, sulfate, the chloride channel inhibitor 5-nitro-2-[(3-phenylpropyl)amino]-benzoate, and several transport site and translocation inhibitors of bicarbonate exchangers. In addition, the CFTR inhibitor GlyH-101 and the SLC4 inhibitors DIDS, SITS, and phloretin exhibited partial inhibition of SLC26A9-mediated Pi uptake. The endogenous expressions of both SLC26A7 and SLC26A9 in the renal cell lines LLC-PK1 and MDCK were primarily intracellular, colocalizing with endosomes, lysosomes, and the trans-Golgi network markers. Conversely, plasma membrane expression was found to be minimal. Pi transport in MDCK cells was sodium-independent, but when either SLC26A7 or SLC26A9 was overexpressed, sodium-activated Pi uptake was observed, along with increased expressions of SLC26A7 or SLC26A9 in the plasma membrane. Conclusions: Sodium-activated Pi transport is a novel function of the SLC26A7 and SLC26A9 multifunctional anion transporters. Further research is necessary to ascertain the relevance to Pi homeostasis in vivo.

Source: Physiologia

DOI: 10.3390/physiologia6020039

Authors: Gema Chopo-Escuin, Jorge A. Quílez, Cecilia Sosa, Natalia Guillén, Víctor Sorribas

Institution: Universidad de Zaragoza

Language: English

Topic: Ion Transport and Channel Regulation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,207