HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chairoungdua, A. Articles by Kanai, Y. Search for Related Content PubMed PubMed Citation Articles by Chairoungdua, A. Articles by Kanai, Y. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 41, 28845-28848, October 8, 1999

COMMUNICATION
Identification of an Amino Acid Transporter Associated with the Cystinuria-related Type II Membrane Glycoprotein^*

Arthit Chairoungdua^§, Hiroko Segawa^§¶, Ju Young Kim, Ken-ichi Miyamoto^¶, Hiromi Haga^**, Yoshihiro Fukui^**, Ken'ichi Mizoguchi, Haruo Ito, Eiji Takeda^¶, Hitoshi Endou, and Yoshikatsu Kanai^§§¶¶

From the  Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, the ^¶ Department of Clinical Nutrition and ^** Department of Anatomy, School of Medicine, Tokushima University, Kuramoto-Cho 3, Tokushima 770-8503, the  Department of Urology, School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba 260-8677, and ^§§ PRESTO, Japan Science and Technology Corporation (JST), Japan

	ABSTRACT

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS DISCUSSION REFERENCES

We identified an amino acid transporter that is associated with the cystinuria-related type II membrane glycoprotein, rBAT (related to b^0,+ amino acid transporter). The transporter designated BAT1 (b^0,+-type amino acid transporter 1) from rat kidney was found to be structurally related to recently identified amino acid transporters for system L, system y⁺L, and system xC, which are linked, via a disulfide bond, to the other type II membrane glycoprotein, 4F2hc (4F2 heavy chain). In the nonreducing condition, a 125-kDa band, which seems to correspond to the heterodimeric complex of BAT1 and rBAT, was detected in rat kidney with anti-BAT1 antibody. The band was shifted to 41 kDa in the reducing condition, confirming that BAT1 and rBAT are linked via a disulfide bond. The BAT1 and rBAT proteins were shown to be colocalized in the apical membrane of the renal proximal tubules where massive cystine transport had been proposed. When expressed in COS-7 cells with rBAT, but not with 4F2hc, BAT1 exhibited a Na⁺-independent transport of cystine as well as basic and neutral amino acids with the properties of system b^0,+. The results from the present investigation were used to establish a family of amino acid transporters associated with type II membrane glycoproteins.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS DISCUSSION REFERENCES

Two type II membrane glycoproteins with single transmembrane domains have been implicated in amino acid transport via the plasma membrane (1). The first is rBAT¹ (related to b^0,+ amino acid transporter), which is also known as D2 or NBAT (2-4). It induces the Na⁺-independent transport of cystine as well as basic and neutral amino acids with the properties of system b^0,+ when expressed in Xenopus oocytes. rBAT was found to be related to the genetic disease cystinuria, in which defects in amino acid reabsorption in the renal proximal tubules lead to urinary loss of cystine and basic amino acids (5). Because rBAT is not typical of transporters with multiple transmembrane structures, it was proposed that rBAT itself is not a transporter but is associated with unidentified amino acid transporters to activate them (1). The second one is 4F2hc (the heavy chain of the 4F2 antigen), which was originally identified as a cell surface antigen that is up-regulated upon lymphocyte activation (6, 7). Because of the amino acid sequence similarity between rBAT and 4F2hc, experiments were performed in which 4F2hc is expressed in Xenopus oocytes to show that 4F2hc also induces amino acid transport (8, 9).

The 4F2 antigen is a heterodimeric complex composed of two subunits, a heavy chain and a light chain that are linked via a disulfide bond (6, 7). Recently, by performing expression cloning, we identified a 4F2 light chain to be an amino acid transporter (10). Transporters for amino acid transport systems L, y⁺L and xC were shown to be 4F2 light chains which require 4F2hc for their functional expression (10-18).

We report here the identification of the first rBAT-associated transporter. It is structurally related to 4F2hc-associated transporters, thereby establishing a family of amino acid transporters associated with type II membrane glycoproteins.

	EXPERIMENTAL PROCEDURES

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS DISCUSSION REFERENCES

cDNA Cloning-- The cDNA for a mouse expressed sequence tag (GenBank^TM/EBI/DDBJ accession number AA162896) showing nucleotide sequence similarity to rat LAT1 was obtained from the integrated and molecular analysis of genomes and their expression. The ~0.8-kb EcoRI fragment was excised from the cDNA (IMAGE cDNA clone number 578502) and labeled with [³²P]dCTP (^T7Quick Prime, Amersham Pharmacia Biotech) for use as a probe for screening a cDNA library prepared from rat kidney poly(A)⁺ RNA using Superscript Choice System (Life Technologies, Inc.) (19, 20). Screening of the cDNA library and isolation of positive plaques were performed as described (19, 20). The cDNA was sequenced in both directions by the dye terminator cycle sequencing method (Perkin-Elmer and Applied Biosystems). Transmembrane regions of proteins were predicted based on SOSUI algorithm (15, 21).

Northern Analysis-- High stringency Northern blot analysis of rat poly(A)⁺ RNA (3 µg/lane) was performed as described previously (10, 22). The EcoRI fragment of BAT1 cDNA corresponding to 1-793 base pairs was labeled with ³²P using ^T7Quick Prime kit (Amersham Pharmacia Biotech).

Anti-peptide Antibody-- Oligopeptides (QMLMEVVPPEKDPEC) corresponding to amino acid residues 474-487 of BAT1 and (SDVDTHAVSLEKGEC) to amino acid residues 629-642 of rat rBAT (2) were synthesized. The C-terminal cysteine residues were introduced for conjugation with keyhole limpet hemocyanine. Anti-peptide antibodies were produced as described elsewhere (23). For immunohistochemical analysis, antisera were affinity-purified as described previously (24).

Western Blotting-- Kidney membranes were prepared as described elsewhere (25). Protein samples were heated at 100 °C for 5 min in sample buffer in either the presence or absence of 5% 2-mercaptoethanol and subjected to sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (26). The separated proteins were transferred electrophoretically to a Hybond-P polyvinylidene difluoride transfer membrane (Amersham Pharmacia Biotech). The membrane was treated with diluted anti-rBAT antiserum (1:40,000) or anti-BAT1 antiserum (1:4,000), and then with horseradish peroxidase-conjugated anti-rabbit IgG as the secondary antibody (Jackson ImmunoResearch Laboratories, Inc.) (26). The signal was detected by an ECL plus system (Amersham Pharmacia Biotech). To verify the specificity of immunoreactions by absorption experiments, the membranes were treated with primary antibodies in the presence of antigen peptides (50 µg/ml).

Immunohistochemistry-- Immunohistochemical analysis of rat kidney was performed as described elsewhere (24) with minor modifications. For immunostaining, serial sections (3 µm) were incubated with affinity-purified anti-rBAT (1:5,000) or anti-BAT1 (1:5,000) antibodies overnight at 4 °C. Thereafter, they were treated with Envision (+) rabbit peroxidase (Dako) for 30 min. To detect immunoreactivity, the sections were treated with diaminobenzidine (0.8 mM) (27).

Functional Expression-- cDNAs for BAT1, rBAT, and 4F2hc were subcloned into the mammalian expression vector pcDNA3.1 (Invitrogen). These plasmids were transfected solely or cotransfected to COS-7 cells by electroporation. For the electroporation, a cell suspension (800 µl, 1.25 × 10⁷ cells/ml) was mixed with plasmids (10 µg for each). The mixture was electroporated at 200 V, 960 microfarads in a 0.4-cm cuvette using a Gene Pulsar (Bio-Rad). Cells were seeded on 24-well culture plates (5 × 10⁵ cells/well) and grown in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum.

For amino acid uptake measurements, cells were used three days after plating (90~100% confluence) on 24-well plates. Dulbecco's modified phosphate-buffered saline (Dulbecco's PBS) containing ¹⁴C-amino acids was added after preincubation of the cells in Dulbecco's PBS for 10 min at 37 °C. The reaction was terminated by removing the uptake medium followed by washing three times with ice-cold Dulbecco's PBS. Then, the cells were solubilized with 0.1 N NaOH, and radioactivity was counted. Because [¹⁴C]cystine (100 µM) uptake was linearly dependent on the incubation time up to 5 min, for all the experiments, uptakes were measured for 2 min, and the values were expressed as picomoles/milligram protein/minute. K_m and V_max of amino acid substrates were determined using the Eadie-Hofstee equation based on the BAT1-mediated amino acid uptakes measured at 3, 10, 30, 100, 300, and 1,000 µM. The BAT1-mediated amino acid uptakes were calculated as differences between the means of uptakes of the COS-7 cells transfected with cDNAs and those of the mock-transfected controls.

For the measurements of the uptake of radiolabeled amino acids in the present study, four wells were used for each data point. Each data point in the figures represents the mean ± S.E. of uptake values (n = 4). To confirm the reproducibility of the results, three separate experiments were performed for each measurement using different batches of COS-7 cell transfectants except for K_m and V_max determination. The results from representative experiments are shown in the figures.

	RESULTS

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS DISCUSSION REFERENCES

Structural Features of BAT1-- A cDNA clone with a 1,746-base pair insert was isolated from rat kidney cDNA library. It contained an open reading frame from nucleotides 170 to 1,630 encoding a 487-amino acid protein designated BAT1 (b^0,+-type amino acid transporter 1). The amino acid sequence of BAT1 exhibited remarkable homology to those of rat system L transporters LAT1 (43% identity) (10) and LAT2 (43%) (15), human y⁺L transporters y⁺LAT1 (42%) (16) and KIAA0245/y⁺LAT2 (44%) (16), and a mouse system xC transporter xCT (43%) (18). The amino acid sequence of BAT1 also exhibited significant homology to those of system y⁺ transporters CAT1~4 (~30%) from mice and humans (5). As shown in Fig. 1, 12 transmembrane regions were predicted from the amino acid sequence. There is a conserved cysteine residue (BAT1 amino acid residue 144) in the putative extracellular loop between predicted transmembrane domains 3 and 4 (28).

View larger version (26K): [in this window] [in a new window]   Fig. 1.   Deduced amino acid sequence of BAT1. The predicted transmembrane regions of BAT1 numbered 1~12 are shown by lines above the sequence. A potential tyrosine kinase-dependent phosphorylation site is located at residue 99 (indicated by #). Protein kinase C-dependent phosphorylation sites are predicted at residues 5, 51, 169, 345, and 399, among which those at residues 5 and 345 are predicted to be located intracellularly (indicated by *). A potential cAMP-dependent phosphorylation site is located at residue 350.

Tissue Distribution and Localization of Expression-- In Northern blot analysis, a 1.9-kb message was expressed in kidney, jejunum, and ileum for BAT1 (Fig. 2A). In the immunohistochemical analysis of rat kidney tissue, BAT1 immunoreactivity was detected in the apical membrane of the proximal tubules (Fig. 2B, left panel). It was stronger in the proximal convoluted tubules than in the proximal straight tubules, with faint but significant immunostaining detected in the proximal straight tubules (Fig. 2B, left panel: arrow). rBAT immunoreactivity was also detected in the apical membrane of the proximal tubules (Fig. 2B, right panel). The expression of rBAT was strongest in the proximal straight tubules. The expression of rBAT was still detected in the convoluted portion of the proximal tubules (Fig. 2B, right panel: arrowhead), although it was weak compared with that in the straight portion (Fig. 2B, right panel: arrow). Colocalization of BAT1 and rBAT proteins was demonstrated in the apical membrane, in particular, in the convoluted portion of the proximal tubules (Fig. 2B, right and left panels: arrowhead).

View larger version (88K): [in this window] [in a new window]   Fig. 2.   Tissue distribution and localization of expression. A, result of high stringency Northern blot analysis using a BAT1 probe on poly(A)+ RNA from rat tissues. A single hybridizing band at 1.9 kb was detected in kidney, jejunum, and ileum. B, results of immunohistochemical analysis of rat kidney serial sections (3 µm) showing the localization of BAT1 (left) and rBAT proteins (right). Both BAT1 and rBAT proteins are located on the apical membrane of the proximal tubules. Colocalization of both proteins was demonstrated in the apical membrane, in particular, in the convoluted portion of the proximal tubules. Arrowheads indicate the start of the proximal convoluted tubule where two proteins are colocalized in the apical membrane. Arrows indicate proximal straight tubules with strong rBAT immunoreactivity and with faint, but significant, BAT1 immunoreactivity.

Protein Characterization under Nonreducing and Reducing Conditions-- Western blot analyses were performed on the membrane fraction prepared from rat kidney in the presence or the absence of 2-mercaptoethanol (Fig. 3A). For BAT1, 251-, 125-, and 38-kDa bands were detected in the absence of 2-mercaptoethanol (nonreducing condition). In the presence of 2-mercaptoethanol (reducing condition), the 251- and 125-kDa bands disappeared, and a 41-kDa band was detected instead. The 38-kDa band seemed to be nonspecific, because it was not affected by the presence of antigen peptides in the absorption experiments, whereas the 251-, 125-, and 41-kDa bands disappeared (Fig. 3A). For rBAT, 231-, 125-, 86-, and 62-kDa bands were detected under the nonreducing condition. Under the reducing condition, the 231- and 125-kDa bands disappeared, and a 90-kDa band was detected instead. The 86- and 62-kDa bands seemed to be nonspecific because they were not affected by the presence of antigen peptides in the absorption experiments (Fig. 3A).

View larger version (24K): [in this window] [in a new window]   Fig. 3.   Association of BAT1 and rBAT. A, Western blot analyses. Western blot analyses were performed on the membrane fraction prepared from rat kidney in the presence or absence of 2-mercaptoethanol. For BAT1 (left), 125- and 251-kDa bands detected in the absence of 2-mercaptoethanol (lane 1) disappeared in the presence 2-mercaptoethanol (lane 2), and a 41-kDa band appeared instead. For rBAT (right), 125- and 231-kDa bands detected in the absence of 2-mercaptoethanol (lane 1) disappeared in the presence 2-mercaptoethanol (lane 2), and a 90-kDa band appeared. Results from the absorption experiments performed under the nonreducing condition are shown in lane 3 for BAT1 and rBAT. The 38-kDa band for BAT1 and 86-kDa band and 62-kDa band for rBAT were not affected by the presence of antigen peptides. B, functional association of BAT1 and rBAT expressed in COS-7 cells. The uptake of [14C]L-cystine (100 µM) was measured on mock-transfected COS-7 cells and COS-7 cells transfected with BAT1, rBAT, 4F2hc, both BAT1 and rBAT, or both BAT1 and 4F2hc. The coexpression of BAT1 with rBAT resulted in a large L-cystine uptake.

Functional Expression in COS-7 Cells-- Because Xenopus oocytes are not suitable for the functional expression of BAT1 due to the abundant expression of endogenous transporters associated with rBAT (2-4), the functional properties of BAT1 were determined by transient expression in COS-7 cells. When BAT1, rBAT, or 4F2hc was solely expressed in COS-7 cells, significant [¹⁴C]L-cystine uptake was not detected compared with mock-transfected controls. Large [¹⁴C]L-cystine uptake was, however, detected when BAT1 was coexpressed with rBAT but not with 4F2hc, indicating that BAT1 requires rBAT, not 4F2hc, for its functional expression (Fig. 3B). Thus, in subsequent experiments to determine the functional characteristics of BAT1, BAT1 was coexpressed with rBAT in COS-7 cells.

BAT1-mediated [¹⁴C]L-cystine uptake was dependent on neither Na⁺ nor Cl (data not shown). The uptake was saturable and followed the Michaelis-Menten kinetics (see below for K_m values). Results from uptake measurements of ¹⁴C-labeled amino acids indicated that BAT1 transported L-cystine, L-lysine, L-arginine, L-ornithine, L-leucine, L-phenylalanine, and L-tyrosine at high levels and other neutral amino acids at low levels (Fig. 4). The uptake values for glycine and proline were particularly low. Acidic amino acids were not transported by BAT1. The K_m/V_max values of BAT1 for L-cystine, L-lysine, L-arginine, L-ornithine, L-leucine, and L-phenylalanine were 305 ± 43.4 µM/1,970 ± 380 pmol/mg of protein/min (mean ± S.E. of three separate experiments), 463 µM/2,990 pmol/mg of protein/min, 203 µM/2,570 pmol/mg of protein/min, 387 µM/2,530 pmol/mg of protein/min, 269 µM/1,330 pmol/mg of protein/min, and 190 µM/1,730 pmol/mg of protein/min, respectively. Consistent with the radiolabeled amino acid uptakes, [¹⁴C]L-cystine uptake was inhibited by L-isomers of cystine as well as basic and neutral amino acids in the experiments in which [¹⁴C]L-cystine uptake (50 µM) was measured in the presence of nonlabeled amino acids (5 mM) (data not shown). System A-selective inhibitor -(aminomethyl)isobutyric acid and system L-selective inhibitor 2-aminobicyclo-(2, 2, 1)-heptane-2-carboxylic acid had no or weak inhibitory effect on [¹⁴C]L-cystine uptake, consistent with the properties of system b^0,+.

View larger version (31K): [in this window] [in a new window]   Fig. 4.   Substrate selectivity of BAT1-mediated transport. The uptakes of 100 µM radiolabeled L-amino acids were measured on COS-7 cells transfected with BAT1 and rBAT. Cystine as well as basic and neutral amino acids were transported by BAT1.

	DISCUSSION

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS DISCUSSION REFERENCES

In the present study, we have identified a novel protein (BAT1) that is structurally related to amino acid transporters for system L, system y⁺L and system xC (10-18). Although these transporters require 4F2hc for their functional expression, we found that BAT1 is associated with rBAT and not with 4F2hc to express its function.

In the Western blot analyses for BAT1 and rBAT, we showed that two corresponding bands (125 and 251 kDa/231 kDa) were detected under the nonreducing condition, whereas under the reducing condition, the bands shifted to smaller sizes, 41 kDa for BAT1 and 90 kDa for rBAT, which corresponded to the sizes of BAT1 and rBAT proteins (2, 3, 29), respectively (Fig. 3A). This suggests that BAT1 and rBAT are linked via disulfide bonds. The 125-kDa band seems to correspond to the heterodimeric complex, whereas the larger bands probably represent multimerized proteins. For transporters that are associated with 4F2hc, it is proposed that a conserved cysteine residue in the extracellular loop between putative transmembrane domains 3 and 4 is responsible for the disulfide bond formation between 4F2hc and transporters (28). The corresponding cysteine residue is also conserved for BAT1 (Cys-144). Because rBAT supports the functional expression of BAT1, whereas 4F2hc does not (Fig. 3B), it is interesting to know what structural feature is responsible for the recognition of partner molecules.

BAT1 is expressed predominantly in kidney and small intestine (Fig. 2A). The pattern of expression of BAT1 correlates well with that of rBAT (2, 3, 22). We were able to demonstrate the colocalization of two proteins in the renal proximal tubules (Fig. 2B). BAT1, as well as rBAT, exists in the apical membrane of the proximal tubules, not in the basolateral membrane where 4F2hc localizes (13, 30, 31), which is consistent with the observation that BAT1 is functionally associated with rBAT and not with 4F2hc (Fig. 3B). The expression of rBAT is the highest in straight convoluted tubules where the expression of BAT1 is fairly low (Fig. 2B) (22, 30, 31). It is, therefore, speculated that still unidentified transporters exist in the proximal tubules, which are associated with rBAT.

When coexpressed with rBAT in COS-7 cells, BAT1 mediates the Na⁺-independent transport of cystine as well as basic and neutral amino acids with the properties of system b^0,+ (32). The substrate selectivity of BAT1 expressed with rBAT in COS-7 cells is basically consistent with that observed when rBAT is solely expressed in Xenopus oocytes where rBAT is assumed to associate with unidentified oocyte endogenous transporters to activate them (2, 3). The K_m values for cystine, lysine, arginine, ornithine, leucine, and phenylalanine lie between ~200 and ~500 µM. Although these values are higher than those measured in Xenopus oocytes expressed solely with rBAT, they are still regarded as high affinity transports (2, 3, 33-35), indicating that the BAT1-rBAT heterodimeric complex is responsible for at least one of the high affinity cystine transport systems in the renal proximal tubules. It has been proposed that the genetic defects of cystine transporters in the renal proximal tubules are responsible for cystinuria (5). The mutation of the rBAT gene was found to be related to autosomal recessive type I cystinuria, whereas type II and type III cystinuria were proposed to be due to mutations of the genes for rBAT-associated transporters (5). It is, therefore, necessary to determine the implications of BAT1 in cystinuria.

In conclusion, we have identified the first rBAT-associated transporter BAT1, which is, surprisingly, structurally related to 4F2hc-associated transporters, thereby establishing a family of amino acid transporters associated with type II membrane glycoproteins. This finding will facilitate the understanding of the mechanisms of molecular association between transporters and their partner type II membrane glycoproteins. The results from the present investigation also suggest the presence of still unidentified transporters that are associated with rBAT.

	ACKNOWLEDGEMENTS

We are grateful to Hisako Ohba and Michi Takahashi for technical assistance. D2/rBAT cDNA was kindly provided by Dr. Matthias A. Hediger, Brigham and Women's Hospital and Harvard Medical School. Anti-BAT1 and anti-rBAT antibodies were supplied by Kumamoto Immunochemical Laboratory Co., Ltd., Kumamoto, Japan.

	FOOTNOTES

^* This work was supported in part by grants from the Ministry of Education, Science, Sports and Culture of Japan (grants-in-aid for Scientific Research and High-Tech Research Center), the Scientific Research Promotion Fund of the Japan Private School Promotion Foundation, the Japan Science and Technology Corporation, the Kato Memorial Bioscience Foundation, the Research Fund of Mitsukoshi Health and Welfare Foundation (1998), the Uehara Memorial Foundation, and the Toyota Physical & Chemical Research Institute.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EMBL Data Bank with accession number(s) AB029559.

^§ These authors contributed equally.

Research fellow of the Japan Society for the Promotion of Science.

^¶¶ To whom correspondence should be addressed: Dept. of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan. Tel.: 81-422-47-5511 (ext. 3453); Fax: 81-422-79-1321.

	ABBREVIATIONS

The abbreviations used are: rBAT, related to b^0,+ amino acid transporter; 4F2hc, 4F2 heavy chain; kb, kilobase pair(s); PBS, phosphate-buffered saline.

	REFERENCES

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS DISCUSSION REFERENCES

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				E. R. Gilbert, E. A. Wong, and K. E. Webb Jr. BOARD-INVITED REVIEW: Peptide absorption and utilization: Implications for animal nutrition and health J Anim Sci, September 1, 2008; 86(9): 2135 - 2155. [Abstract] [Full Text] [PDF]

				S. F. Liao, E. S. Vanzant, J. A. Boling, and J. C. Matthews Identification and expression pattern of cationic amino acid transporter-1 mRNA in small intestinal epithelia of Angus steers at four production stages J Anim Sci, March 1, 2008; 86(3): 620 - 631. [Abstract] [Full Text] [PDF]

				E. R. Gilbert, H. Li, D. A. Emmerson, K. E. Webb Jr, and E. A. Wong Dietary Protein Quality and Feed Restriction Influence Abundance of Nutrient Transporter mRNA in the Small Intestine of Broiler Chicks J. Nutr., February 1, 2008; 138(2): 262 - 271. [Abstract] [Full Text] [PDF]

				S. Broer Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia Physiol Rev, January 1, 2008; 88(1): 249 - 286. [Abstract] [Full Text] [PDF]

				K. Kaira, N. Oriuchi, Y. Otani, K. Shimizu, S. Tanaka, H. Imai, N. Yanagitani, N. Sunaga, T. Hisada, T. Ishizuka, et al. Fluorine-18-{alpha}-Methyltyrosine Positron Emission Tomography for Diagnosis and Staging of Lung Cancer: A Clinicopathologic Study Clin. Cancer Res., November 1, 2007; 13(21): 6369 - 6378. [Abstract] [Full Text] [PDF]

				M. Font-Llitjos, L. Feliubadalo, M. Espino, R. Cleries, S. Manas, I. M. Frey, S. Puertas, G. Colell, S. Palomo, J. Aranda, et al. Slc7a9 knockout mouse is a good cystinuria model for antilithiasic pharmacological studies Am J Physiol Renal Physiol, September 1, 2007; 293(3): F732 - F740. [Abstract] [Full Text] [PDF]

				V. Cerec, C. Piquet-Pellorce, H. A.A. Aly, A.-M. Touzalin, B. Jegou, and F. Bauche Multiple Pathways for Cationic Amino Acid Transport in Rat Seminiferous Tubule Cells Biol Reprod, February 1, 2007; 76(2): 241 - 249. [Abstract] [Full Text] [PDF]

				S. Kaneko, A. Ando, E. Okuda-Ashitaka, M. Maeda, K. Furuta, M. Suzuki, M. Matsumura, and S. Ito Ornithine Transport Via Cationic Amino Acid Transporter-1 Is Involved in Ornithine Cytotoxicity in Retinal Pigment Epithelial Cells Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 464 - 471. [Abstract] [Full Text] [PDF]

				T. Verri, C. Dimitri, S. Treglia, F. Storelli, S. De Micheli, L. Ulianich, P. Vito, S. Marsigliante, C. Storelli, and B. Di Jeso Multiple pathways for cationic amino acid transport in rat thyroid epithelial cell line PC Cl3 Am J Physiol Cell Physiol, February 1, 2005; 288(2): C290 - C303. [Abstract] [Full Text] [PDF]

				H. Quan, K. Athirakul, W. C. Wetsel, G. E. Torres, R. Stevens, Y. T. Chen, T. M. Coffman, and M. G. Caron Hypertension and Impaired Glycine Handling in Mice Lacking the Orphan Transporter XT2 Mol. Cell. Biol., May 15, 2004; 24(10): 4166 - 4173. [Abstract] [Full Text] [PDF]

				L. Feliubadalo, M. L. Arbones, S. Manas, J. Chillaron, J. Visa, M. Rodes, F. Rousaud, A. Zorzano, M. Palacin, and V. Nunes Slc7a9-deficient mice develop cystinuria non-I and cystine urolithiasis Hum. Mol. Genet., September 1, 2003; 12(17): 2097 - 2108. [Abstract] [Full Text] [PDF]

				P. Jutabha, Y. Kanai, M. Hosoyamada, A. Chairoungdua, D. K. Kim, Y. Iribe, E. Babu, J. Y. Kim, N. Anzai, V. Chatsudthipong, et al. Identification of a Novel Voltage-driven Organic Anion Transporter Present at Apical Membrane of Renal Proximal Tubule J. Biol. Chem., July 18, 2003; 278(30): 27930 - 27938. [Abstract] [Full Text] [PDF]

				E. Fernandez, D. Torrents, J. Chillaron, R. Martin del Rio, A. Zorzano, and M. Palacin Basolateral LAT-2 Has a Major Role in the Transepithelial Flux of L-Cystine in the Renal Proximal Tubule Cell Line OK J. Am. Soc. Nephrol., April 1, 2003; 14(4): 837 - 847. [Abstract] [Full Text] [PDF]

				C. Bauch, N. Forster, D. Loffing-Cueni, V. Summa, and F. Verrey Functional Cooperation of Epithelial Heteromeric Amino Acid Transporters Expressed in Madin-Darby Canine Kidney Cells J. Biol. Chem., January 3, 2003; 278(2): 1316 - 1322. [Abstract] [Full Text] [PDF]

				E. Fernandez, M. Carrascal, F. Rousaud, J. Abian, A. Zorzano, M. Palacin, and J. Chillaron rBAT-b0,+AT heterodimer is the main apical reabsorption system for cystine in the kidney Am J Physiol Renal Physiol, September 1, 2002; 283(3): F540 - F548. [Abstract] [Full Text] [PDF]

				C. Bauch and F. Verrey Apical heterodimeric cystine and cationic amino acid transporter expressed in MDCK cells Am J Physiol Renal Physiol, July 1, 2002; 283(1): F181 - F189. [Abstract] [Full Text] [PDF]

				H. Matsuo, Y. Kanai, J. Y. Kim, A. Chairoungdua, D. K. Kim, J. Inatomi, Y. Shigeta, H. Ishimine, S. Chaekuntode, K. Tachampa, et al. Identification of a Novel Na+-independent Acidic Amino Acid Transporter with Structural Similarity to the Member of a Heterodimeric Amino Acid Transporter Family Associated with Unknown Heavy Chains J. Biol. Chem., May 31, 2002; 277(23): 21017 - 21026. [Abstract] [Full Text] [PDF]

				H. Segawa, I. Kaneko, A. Takahashi, M. Kuwahata, M. Ito, I. Ohkido, S. Tatsumi, and K.-i. Miyamoto Growth-related Renal Type II Na/Pi Cotransporter J. Biol. Chem., May 24, 2002; 277(22): 19665 - 19672. [Abstract] [Full Text] [PDF]

				J. Chillaron, R. Roca, A. Valencia, A. Zorzano, and M. Palacin Heteromeric amino acid transporters: biochemistry, genetics, and physiology Am J Physiol Renal Physiol, December 1, 2001; 281(6): F995 - F1018. [Abstract] [Full Text] [PDF]

				E. C. H. Friesema, R. Docter, E. P. C. M. Moerings, F. Verrey, E. P. Krenning, G. Hennemann, and T. J. Visser Thyroid Hormone Transport by the Heterodimeric Human System L Amino Acid Transporter Endocrinology, October 1, 2001; 142(10): 4339 - 4348. [Abstract] [Full Text] [PDF]

				C. A. Wagner, F. Lang, and S. Broer Function and structure of heterodimeric amino acid transporters Am J Physiol Cell Physiol, October 1, 2001; 281(4): C1077 - C1093. [Abstract] [Full Text] [PDF]

B. P. Bode Recent Molecular Advances in Mammalian Glutamine Transport J. Nutr., September 1, 2001; 131(9): 2475S - 2485. [Abstract] [Full Text] [PDF]