Cloning and characterization of the transport modifier RS1 from rabbit which was previously assumed to be specific for Na+-D-glucose cotransport

previously we cloned membrane associated polypeptides from pig and man (pRS 1, hRS1) which altered rate and glucose dependence of Na+-D-glucose cotrans port expressed by SGLT1 from rabbit and man. This paper describes the cloni ng of a related cDNA sequence from rabbit intestine (rbRS1) which encodes a gene product with about 65% amino acid identity to pRS1 and hRS1. Hybridiz ation of endonuclease-restricted genomic DNA with cDNA fragments of rbRS1 s howed that there is only one gene with similarity to rbRS1 in rabbit, and g enomic PCR amplifications revealed that the rbRS1 gene is intronless, Compa ring the transcription of rbRS1 and rbSGLT1 in various tissues and cell typ es, different mRNA patterns were obtained for both genes. In Xenopus oocyte s the V-max of expressed Na+-D-glucose cotransport was increased or decreas ed when rbRS1 was coexpressed with rbSGLT1 or hSGLT1, respectively. After c oexpression with hSGLT1 the glucose dependence of the expressed transport w as changed. By coexpression of rbRS1 with the human organic cation transpor ter hOCT2 the expressed cation uptake was not altered; however, the express ed cation uptake was drastically decreased when hRS1 was coexpressed with h OCT2. The data show that RS1 can modulate the function of transporters with nonhomologous primary structures. (C) 1999 Elsevier Science B.V. All right s reserved.