C-terminal truncations of the renal cystine transporter (NBAT): A B i modal pattern of functional expression
Phospholipid Transfer Proteins
NBAT induces Na +-independent transport of cationic and neutral amino acids, including cystine, in Xenopus oocytes. Mutations in human NBAT occur in Type I cystinurics. Renal NBAT is found in association with a 45-50 kDa protein; the heterodimer is the presumed functional unit of the transporter. In oocytes, NBAT induces transport presumably by complexing with oocyte protein(s). To evaluate the role of various regions of NBAT, we made a series of C-terminally truncated mutants of rat NBAT ( 683 aa). These mutants in oocytes, interestingly, exhibit a bimodal pattern of transport activity. Deletion of 68 C-terminal residues resulted in attenuation of transport. However, further truncation (A588-683) restored the ability to induce transport that was similar to that induced by the wild-type (WT) NBAT. Further truncations of this mutant abolished transport activity. Although WT/NBAT and the A588-683 mutant expressed similar transport systems, the two forms were affected in strikingly different manner by a point mutation (C111S). Models to explain these results will be discussed.