Expression of heteromeric amino acid transporters along the murine intestine.
Members of the new heterodimeric amino acid transporter family are composed of two subunits, a catalytic multitransmembrane spanning 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 b degrees (,+)AT to form a cystine and cationic amino acid transporter. The other heavy chain, 4F2hc, can interact with seven 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 b degrees (,+)AT subunit result in cystinuria whereas a defect in the 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 coexpression of 4F2hc, LAT2 and y(+)-LAT1 in stomach and small intestine, whereas rBAT and b degrees (,+)AT were found colocalizing 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, b degrees (,+)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.
Dave
Mital H
MH
Institute of Physiology, University of Zurich, Winterthurerstr. 190, CH-8057 Zurich, Switzerland.
Schulz
Nicole
N
Zecevic
Marija
M
Wagner
Carsten A
CA
Verrey
Francois
F
D020157:Amino Acid Transport Disorders, Inborn / Q000378:metabolism* / Q000503:physiopathology; D026905:Amino Acid Transport Systems / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D003555:Cystinuria / Q000378:metabolism* / Q000503:physiopathology; D019281:Dimerization; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D008239:Lysine / Q000652:urine; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
D026905:Amino Acid Transport Systems; D012333:RNA, Messenger; D008239:Lysine