Renal localization and regulation by dietary phosphate of the MCT14 orphan transporter

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.