title: Functional cooperation of epithelial heteromeric amino acid transporters expressed in madin-darby canine kidney cells.
abstract: The heteromeric amino acid transporters b(0,+)AT-rBAT (apical), y(+)LAT1-4F2hc, and possibly LAT2-4F2hc (basolateral) participate to the (re)absorption of cationic and neutral amino acids in the small intestine and kidney proximal tubule. We show now by immunofluorescence that their expression levels follow the same axial gradient along the kidney proximal tubule (S1>S2S3). We reconstituted their co-expression in MDCK cell epithelia and verified their polarized localization by immunofluorescence. Expression of b(0,+)AT-rBAT alone led to a net reabsorption of l-Arg (given together with l-Leu). Coexpression of basolateral y(+)LAT1-4F2hc increased l-Arg reabsorption and reversed l-Leu transport from (re)absorption to secretion. Similarly, l-cystine was (re)absorbed when b(0,+)AT-rBAT was expressed alone. This net transport was further increased by the coexpression of 4F2hc, due to the mobilization of LAT2 (exogenous and/or endogenous) to the basolateral membrane. In summary, apical b(0,+)AT-rBAT cooperates with y(+)LAT1-4F2hc or LAT2-4F2hc for the transepithelial reabsorption of cationic amino acids and cystine, respectively. The fact that the reabsorption of l-Arg led to the secretion of l-Leu demonstrates that the implicated heteromeric amino acid transporters function in epithelia as exchangers coupled in series and supports the notion that the parallel activity of unidirectional neutral amino acid transporters is required to drive net amino acid reabsorption.
authors.affiliation: Institute of Physiology and Institute of Anatomy, University of Zürich, Winterthurerstrasse 190, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Bauch
authors.forename: Natasha
authors.initials: N
authors.lastname: Forster
authors.forename: Dominique
authors.initials: D
authors.lastname: Loffing-Cueni
authors.forename: Vanessa
authors.initials: V
authors.lastname: Summa
authors.forename: François
authors.initials: F
authors.lastname: Verrey
mesh_terms: D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology*; D002460:Cell Line; D003553:Cystine / Q000378:metabolism; D004285:Dogs; D027301:Fusion Regulatory Protein 1, Light Chains / Q000032:analysis / Q000502:physiology*; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D027283:Large Neutral Amino Acid-Transporter 1 / Q000032:analysis / Q000502:physiology*; D007930:Leucine / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D051379:Mice
chemical_list: D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D027301:Fusion Regulatory Protein 1, Light Chains; D027283:Large Neutral Amino Acid-Transporter 1; D008562:Membrane Glycoproteins; C499488:Slc7a9 protein, mouse; D003553:Cystine; D001120:Arginine; D007930:Leucine