Evidence that the transport-related proteins BAT and 4F2hc are not specific for amino acids: induction of Na+-dependent uridine and pyruvate transport activity by recombinant BAT and 4F2hc expressed in Xenopus oocytes

Members of the BAT and 4F2hc gene family have one or, in the case of BAT, u p to four transmembane domains and induce amino acid transport systems b(0, +) (BAT) and y(+)L (4F2hc) when expressed in Xenopus oocytes. System b(0,+) is a Na+-independent process with a broad tolerance for cationic and zwitt erionic amino acids, whereas y(+)L exhibits Na+-independent transport of ca tionic amino acids (e.g., lysine) and Nac-dependent transport of zwitterion ic amino acids (e.g., leucine). Mutations in the human BAT gene are associa ted with type I cystinuria, a genetic disease affecting the ability of inte stinal and renal brush border membranes to transport cationic amino acids a nd cystine. An unresolved question is whether BAT and 4F2hc themselves have catalytic (i.e., transporting) activity or whether they operate as activat ors of other, as yet unidentified, transporter proteins. In this report, we have investigated the transport of representatives of four different class es of organic substrates in Xenopus oocytes following injection with rat BA T or 4F2hc RNA transcripts: leucine (a control amino acid substrate), uridi ne (a nucleoside), pyruvate (a monocarboxylate), and choline (an amine). Bo th recombinant proteins induced small, statistically significant Na+-depend ent fluxes of uridine and pyruvate but had no effect on choline uptake. In contrast, control oocytes injected with transcripts for conventional nucleo side and cationic aminoacid transporters (rat CNT1 and murine CAT1, respect ively) showed no induction of transport of either leucine or pyruvate (CNT1 ) or uridine or pyruvate (CAT1). These findings support the idea that BAT a nd 4F2hc are transport activators and minimize the possibility that they ha ve intrinsic transport capability. The transport-regulating functions of th ese proteins may extend to permeants other than amino acids.