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Received March 21, 2004
Revised April 5, 2004
Accepted after revision May 19, 2004
1 Institute of Physiology, University of Zurich
2 University of Zurich
* To whom correspondence should be addressed. E-mail: wagnerca{at}access.unizh.ch.
Members of the new heterodimeric amino acid transporter family are comprised of two subunits, a catalytic multi-transmembrane spanning membrane protein (light chain) and a type II glycoprotein (heavy chain). These transporters function as exchangers and thereby extend the transmembrane amino acid transport selectivity to specific amino acids. The heavy chain rBAT associates with the light chain b0,+AT to form a cystine and cationic amino acid transporter. The other heavy chain, 4F2hc, can interact with 7 different light chains to form various transporters corresponding to systems L, y+L, asc or x-c. The importance of some of these transporters in intestinal and renal (re)absorption of amino acids is highlighted by the fact that mutations in either the rBAT or b0,+AT subunit result in cystinuria whereas a defect in y+-LAT1 light chain causes lysinuric protein intolerance. Here we investigated the localization of these transporters in intestine since both diseases are also characterized by altered intestinal amino acid absorption. Real time PCR showed organ-specific expression patterns for all transporter subunit mRNAs along the intestine and Western blotting confirmed these findings on the protein level. Immunohistochemistry demonstrated basolateral co-expression of 4F2hc, LAT2 and y+-LAT-1 in stomach and small intestine, whereas rBAT and b0,+AT were found co-localizing on the apical side of small intestine epithelium. In stomach, 4F2hc and LAT2 were localized in H+/K+-ATPase-expressing parietal cells. The abundant expression of several members of the heterodimeric transporter family along the murine small intestine suggests their involvement in amino acids absorption. Furthermore, strong expression of rBAT, b0,+AT and y+-LAT1 in the small intestine explains the reduced intestinal absorption of some amino acid in patients with cystinuria or lysinuric protein intolerance.
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