Differential Influence of the 4F2 Heavy Chain and the Protein Related to b0,+ Amino Acid Transport on Substrate Affinity of the Heteromeric b0,+ Amino Acid Transporter (original) (raw)

2000, Journal of Biological Chemistry

We provide evidence here that b 0,؉ amino acid transporter (b 0,؉ AT) interacts with 4F2 heavy chain (4F2hc) as well as with the protein related to b 0,؉ amino acid transporter (rBAT) to constitute functionally competent b 0,؉-like amino acid transport systems. This evidence has been obtained by co-expression of b 0,؉ AT and 4F2hc or b 0,؉ AT and rBAT in human retinal pigment epithelial cells and in COS-1 cells. The ability to interact with 4F2hc and rBAT is demonstrable with mouse b 0,؉ AT as well as with human b 0,؉ AT. Even though both the 4F2hc⅐b 0,؉ AT complex and the rBAT⅐b 0,؉ AT complex exhibit substrate specificity that is characteristic of system b 0,؉ , these two complexes differ significantly in substrate affinity. The 4F2hc⅐b 0,؉ AT complex has higher substrate affinity than the rBAT⅐b 0,؉ AT complex. In situ hybridization studies demonstrate that the regional distribution pattern of mRNA in the kidney is identical for b 0,؉ AT and 4F2hc. The pattern of rBAT mRNA expression is different from that of b 0,؉ AT mRNA and 4F2hc mRNA, but there are regions in the kidney where b 0,؉ AT mRNA expression overlaps with rBAT mRNA expression as well as with 4F2hc mRNA expression. The heavy chain of the 4F2 cell surface antigen (4F2hc) 1 and the protein related to the b 0,ϩ amino acid transporter (rBAT) are type II membrane glycoproteins with membrane topology atypical to most of the known transporters (1). However, these two proteins have been recently shown to be obligatory for the function of several amino acid transport systems. 4F2hc interacts with different proteins to constitute distinct amino acid transport activities. The 4F2hc-associated amino acid transport proteins thus far identified are LAT1 and LAT2, which are responsible for system L (2-6), y ϩ LAT1 and y ϩ LAT2, which are responsible for system y ϩ L (7, 8), xCT, which is responsible for system x c Ϫ (9), and b 0,ϩ AT (also called 4F2-1c6), which is responsible for system b 0,ϩ (10). The interaction between 4F2hc and b 0,ϩ AT to constitute the amino acid transport system b 0,ϩ , reported from our laboratory recently (10), was an unexpected finding because available evidence suggests that only rBAT is