抄録
Twelve-membrane-spanning amino acid transporters of SLC (solute carrier) 7 family require single membrane spanning proteins for their proper membrane targeting. Two single membrane spanning accessory units 4F2hc and rBAT are identified so far in SLC3 family. They are connected to the specific 12-membrane-spanning catalytic units via a disulfide bond and form heterodimeric transporters. In the epithelial cells of small intestine and renal proximal tubules, rBAT is localized in the apical membrane, whereas 4F2hc is found in the basolateral membrane. We performed extensive chimera analysis in which we expressed the chimeric proteins of rBAT and 4F2hc with BAT1, a partner of rBAT, or LAT1, a partner of 4F2hc and found that the single membrane-spanning accessory units recognize their partner catalytic units at the membrane-spanning domains. Furthermore, the accessory units were proved to possess signals responsible for membrane sorting. rBAT is connected with BAT1 and form a cystine transporter on the apical membrane of the epithelia. By analyzing cystinuria patients, we found a loss-of-function mutation in the C-terminus intracellular domain of BAT1. The motif-like sequence with similarity to the "targeting domain" of Cav1.2 turned out to be responsible for the transition from endoplasmic reticulum to Golgi complex and for the membrane targeting of heterodimeric transporters. Based on the deletion analysis and yeast two hybrid analysis, more than one proteins are proposed to interact with the C-terminus of BAT1 and promote the proper membrane targeting of the heterodimeic complex. [Jpn J Physiol 55 Suppl:S7 (2005)]
