CLONING AND FUNCTIONAL EXPRESSION OF A CDNA FROM RAT JEJUNAL EPITHELIUM ENCODING A PROTEIN (4F2HC) WITH SYSTEM Y(-ACID-TRANSPORT ACTIVITY()L AMINO)

Two different protein families, designated CAT (cationic amino acid tr ansporter) and BAT (broad-specificity amino acid transporter) mediate the plasma membrane transport of cationic amino acids in animal cells. CAT transporters have 12-14 transmembrane domains and are selective f or cationic amino acids. BAT proteins, in contrast, have one to four t ransmembrane domains and induce the transport of both cationic and zwi tterionic amino acids when expressed in Xenopus oocytes. Mutations in the human BAT gene cause type I cystinuria, a disease affecting the ab ility of intestinal and renal brush border membranes to transport cati onic amino acids and cystine. We have used functional expression cloni ng in oocytes to isolate a BAT-related cDNA from rat jejunal epitheliu m. The cDNA encodes the rat 4F2 heavy chain (4F2hc) cell-surface antig en, a 527-residue (60 kDa) protein that is 26%, identical in amino aci d sequence with rat renal BAT (also known as NBAT/D2). Expression of r at jejunal 4F2hc in oocytes induced the lysine-inhibitable Na+-depende nt influx of leucine and the leucine-inhibitable Na+-independent influ x of lysine. Lysine efflux was stimulated by extracellular (Nat plus l eucine). These characteristics identify the expressed amino acid trans port activity as system y(+)L, a transporter that has been implicated in basal membrane transport of cationic amino acids in intestine, kidn ey and placenta.