The light subunit of system b^o,+ is fully functional in the absence of the heavy subunit

The heteromeric amino acid transporters are composed of a type II glycoprotein and a non-glycosylated polytopic membrane protein. System b^o,+ exchanges dibasic for neutral amino acids. It is composed of rBAT and b^o,+AT, the latter being the polytopic membrane subunit. Mutations in either of them cause malfunction of the system, leading to cystinuria. b^o,+AT-reconstituted systems from HeLa or MDCK cells catalysed transport of arginine that was totally dependent on the presence of one of the b^o,+ substrates inside the liposomes. rBAT was essential for the cell surface expression of b^o,+AT, but it was not required for reconstituted b^o,+AT transport activity. No system b^o,+ transport was detected in liposomes derived from cells expressing rBAT alone. The reconstituted b^o,+AT showed kinetic asymmetry. Expressing the cystinuria-specific mutant A354T of b^o,+AT in HeLa cells together with rBAT resulted in defective arginine uptake in whole cells, which was paralleled by the reconstituted b^o,+AT activity. Thus, subunit b^o,+AT by itself is sufficient to catalyse transmembrane amino acid exchange. The polytopic subunits may also be the catalytic part in other heteromeric transporters.