Cloning and functional expression of a mammalian Na+/nucleoside cotransporter. A member of the SGLT family

Abstract

Complementary DNAs encoding seven different proteins related to the rabbit intestinal Na+/glucose cotransporter, SGLT1, were isolated from a rabbit renal cDNA library at relatively high stringency. The messages for RK-B to RK-F were single mRNA species at 2.3 kilobases (kb) in heart and kidney. The message for RK-A was 4 kb and was found in brain, lung, intestine, liver, and kidney. RK-I mRNA was approximately 3 kb and was found in all tissues tested. The most abundant clone, RK-C, constituted nucleotides 66-2150 of the sodium-nucleoside cotransporter, SNST1. The 672-amino acid protein encoded by SNST1 is 61% identical and 80% similar in sequence to SGLT1. Expression of SNST1c in Xenopus oocytes resulted in nucleoside-stimulated 22Na uptake and sodium-dependent [3H]uridine uptake. The uptake of [3H]uridine was inhibited by a range of nucleosides, including the anti-human immunodeficiency virus drug, dideoxycytidine. The results of this study show that there is a family of SGLT1-related proteins found in a wide variety of tissues and that one of these is a Na+/nucleoside cotransporter.