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Abstract
MCT14 is an orphan transporter belonging to the SLC16 transporter family mediating the transport of monocarboxylates, aromatic amino acids, creatine, and thyroid hormones. The expression, tissue localization, regulation, and function of MCT14 are unknown. In mouse MCT14 mRNA abundance is highest in kidney. Using a newly developed and validated antibody, MCT14 was localized to the luminal membrane of the thick ascending limb of the loop of Henle colocalizing in the same cells with uromodulin and NKCC2. MCT14 mRNA and protein was found to be highly regulated by dietary phosphate intake in mice being increased by high dietary phosphate intake at both mRNA and protein level. In order to identify the transport substrate(s), we expressed MCT14 in Xenopus laevis oocytes where MCT14 was integrated into the plasma membrane. However, no transport was discovered for the classic substrates of the SLC16 family nor for phosphate. In summary, MCT14 is an orphan transporter regulated by phosphate and highly enriched in kidney localizing to the luminal membrane of one specific nephron segment.
Highlights
Inorganic phosphate is a molecule involved in energy metabolism and signaling as well as essential for structural molecules in cells and bone
Hypophosphatemia blunts the production of parathyroid hormone (PTH) [2] and fibroblast growth factor 23 (FGF23) [3], releasing the inhibitory effect of both hormones on renal phosphate cotransporters (NaPi-IIa, NaPi-IIc and PiT-2), enhancing renal reabsorption of phosphate
Dietary alterations in phosphate supply cause a fast response in PTH and later on in vitamin D and FGF23 [4,5], and promote changes in other metabolic pathways such as gluconeogenesis, or altered insulin sensitivity [8], indicating the importance of phosphate in energy metabolism
Summary
Inorganic phosphate is a molecule involved in energy metabolism and signaling as well as essential for structural molecules in cells and bone. We report that the renal expression of MCT14 is regulated by the dietary content of phosphate, the generation and validation of a polyclonal antibody to analyze its segmental distribution in kidney as well as our attempts to identify substrates. Acute and chronic adaptation experiments, transcriptome analysis revealed that the mRNA of Slc16a14 (the gene encoding the monocarboxylate transporter MCT14) was strongly regulated.
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