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Physiol. Rev. 78: 487-545, 1998;
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PHYSIOLOGICAL REVIEWS   Vol. 78 No. 2 April 1998, pp. 487-545
Copyright ©1998 The American Physiological Society

Transporters for Cationic Amino Acids in Animal Cells: Discovery, Structure, and Function

R. DEVÉS AND C. A. R. BOYD

Programa de Fisiología y Biofísica, Instituto de Ciencias Biomédicas, Universidad de Chile, Santiago, Chile; and Department of Human Anatomy and Genetics, University of Oxford, Oxford, United Kingdom

Devés, R., and C. A. R. Boyd. Transporters for Cationic Amino Acids in Animal Cells: Discovery, Structure, and Function. Physiol. Rev. 78: 487-545, 1998. --- The structure and function of the four cationic amino acid transporters identified in animal cells are discussed. The systems differ in specificity, cation dependence, and physiological role. One of them, system y+, is selective for cationic amino acids, whereas the others (B0,+, b0,+, and y+L) also accept neutral amino acids. In recent years, cDNA clones related to these activities have been isolated. Thus two families of proteins have been identified: 1) CAT or cationic amino acid transporters and 2) BAT or broad-scope transport proteins. In the CAT family, three genes encode for four different isoforms [CAT-1, CAT-2A, CAT-2(B) and CAT-3]; these are ~70-kDa proteins with multiple transmembrane segments (-), and despite their structural similarity, they differ in tissue distribution, kinetics, and regulatory properties. System y+ is the expression of the activity of CAT transporters. The BAT family includes two isoforms (rBAT and 4F2hc); these are 59- to 78-kDa proteins with one to four membrane-spanning segments, and it has been proposed that these proteins act as transport regulators. The expression of rBAT and 4F2hc induces system b0,+ and system y+L activity in Xenopus laevis oocytes, respectively. The roles of these transporters in nutrition, endocrinology, nitric oxide biology, and immunology, as well as in the genetic diseases cystinuria and lysinuric protein intolerance, are reviewed. Experimental strategies, which can be used in the kinetic characterization of coexpressed transporters, are also discussed.




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Growth Factors Regulation of Rabbit Sodium-Dependent Neutral Amino Acid Transporter ATB0 and Oligopeptide Transporter 1 mRNAs Expression after Enterectomy
JPEN J Parenter Enteral Nutr, March 1, 2001; 25(2): 65 - 72.
[Abstract] [PDF]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. I. Zharikov, A. A. Sigova, S. Chen, M. R. Bubb, and E. R. Block
Cytoskeletal regulation of the L-arginine/NO pathway in pulmonary artery endothelial cells
Am J Physiol Lung Cell Mol Physiol, March 1, 2001; 280(3): L465 - L473.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
A.C. Mendes Ribeiro, T.M.C. Brunini, J.C. Ellory, and G.E. Mann
Abnormalities in L-arginine transport and nitric oxide biosynthesis in chronic renal and heart failure
Cardiovasc Res, March 1, 2001; 49(4): 697 - 712.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Cell Physiol.Home page
V. Dall'Asta, O. Bussolati, R. Sala, B. M. Rotoli, G. Sebastio, M. P. Sperandeo, G. Andria, and G. C. Gazzola
Arginine transport through system y+L in cultured human fibroblasts: normal phenotype of cells from LPI subjects
Am J Physiol Cell Physiol, December 1, 2000; 279(6): C1829 - C1837.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Cell Physiol.Home page
H. Nawrath, J. W. Wegener, J. Rupp, A. Habermeier, and E. I. Closs
Voltage dependence of L-arginine transport by hCAT-2A and hCAT-2B expressed in oocytes from Xenopus laevis
Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1336 - C1344.
[Abstract] [Full Text] [PDF]


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MicrobiologyHome page
D. L. Jack, I. T. Paulsen, and M. H. Saier
The amino acid/polyamine/organocation (APC) superfamily of transporters specific for amino acids, polyamines and organocations
Microbiology, August 1, 2000; 146(8): 1797 - 1814.
[Abstract] [Full Text]


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Am. J. Physiol. Cell Physiol.Home page
P. T.-Y. Ayuk, C. P. Sibley, P. Donnai, S. D'Souza, and J. D. Glazier
Development and polarization of cationic amino acid transporters and regulators in the human placenta
Am J Physiol Cell Physiol, June 1, 2000; 278(6): C1162 - C1171.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
F. Wu, B. Cholewa, and D. L. Mattson
Characterization of L-arginine transporters in rat renal inner medullary collecting duct
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2000; 278(6): R1506 - R1512.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Renal Physiol.Home page
J. Gloy, S. Reitinger, K.-G. Fischer, R. Schreiber, A. Boucherot, K. Kunzelmann, P. Mundel, and H. Pavenstadt
Amino acid transport in podocytes
Am J Physiol Renal Physiol, June 1, 2000; 278(6): F999 - F1005.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
D. P. Rajan, W. Huang, R. Kekuda, R. L. George, J. Wang, S. J. Conway, L. D. Devoe, F. H. Leibach, P. D. Prasad, and V. Ganapathy
Differential Influence of the 4F2 Heavy Chain and the Protein Related to b0,+ Amino Acid Transport on Substrate Affinity of the Heteromeric b0,+ Amino Acid Transporter
J. Biol. Chem., May 5, 2000; 275(19): 14331 - 14335.
[Abstract] [Full Text] [PDF]


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Hum Mol GenetHome page
J. Mykkanen, D. Torrents, M. Pineda, M. Camps, M. E. Yoldi, N. Horelli-Kuitunen, K. Huoponen, M. Heinonen, J. Oksanen, O. Simell, et al.
Functional analysis of novel mutations in y+LAT-1 amino acid transporter gene causing lysinuric protein intolerance (LPI)
Hum. Mol. Genet., February 12, 2000; 9(3): 431 - 438.
[Abstract] [Full Text] [PDF]


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Mol. Pharmacol.Home page
E. I. Closs, J.-S. Scheld, M. Sharafi, and U. Förstermann
Substrate Supply for Nitric-Oxide Synthase in Macrophages and Endothelial Cells: Role of Cationic Amino Acid Transporters
Mol. Pharmacol., January 1, 2000; 57(1): 68 - 74.
[Abstract] [Full Text]


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Am. J. Physiol. Cell Physiol.Home page
A. A. Ogonowski, W. H. Kaesemeyer, L. Jin, V. Ganapathy, F. H. Leibach, and R. W. Caldwell
Effects of NO donors and synthase agonists on endothelial cell uptake of L-Arg and superoxide production
Am J Physiol Cell Physiol, January 1, 2000; 278(1): C136 - C143.
[Abstract] [Full Text] [PDF]


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Antimicrob. Agents Chemother.Home page
J. D. Walters, F. Zhang, and R. J. Nakkula
Mechanisms of Fluoroquinolone Transport by Human Neutrophils
Antimicrob. Agents Chemother., November 1, 1999; 43(11): 2710 - 2715.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
D. P. Rajan, R. Kekuda, W. Huang, H. Wang, L. D. Devoe, F. H. Leibach, P. D. Prasad, and V. Ganapathy
Cloning and Expression of a b0,+-like Amino Acid Transporter Functioning as a Heterodimer with 4F2hc Instead of rBAT. A NEW CANDIDATE GENE FOR CYSTINURIA
J. Biol. Chem., October 8, 1999; 274(41): 29005 - 29010.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J. L. Sloan and S. Mager
Cloning and Functional Expression of a Human Na+ and Cl--dependent Neutral and Cationic Amino Acid Transporter B0+
J. Biol. Chem., August 20, 1999; 274(34): 23740 - 23745.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
M. Pineda, E. Fernandez, D. Torrents, R. Estevez, C. Lopez, M. Camps, J. Lloberas, A. Zorzano, and M. Palacin
Identification of a Membrane Protein, LAT-2, That Co-expresses with 4F2 Heavy Chain, an L-type Amino Acid Transport Activity with Broad Specificity for Small and Large Zwitterionic Amino Acids
J. Biol. Chem., July 9, 1999; 274(28): 19738 - 19744.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
C. B. Cymeryng, L. A. Dada, C. Colonna, C. F. Mendez, and E. J. Podestá
Effects of L-Arginine in Rat Adrenal Cells: Involvement of Nitric Oxide Synthase
Endocrinology, July 1, 1999; 140(7): 2962 - 2967.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
V. L. Tlapak-Simmons, B. A. Baggenstoss, T. Clyne, and P. H. Weigel
Purification and Lipid Dependence of the Recombinant Hyaluronan Synthases from Streptococcus pyogenes and Streptococcus equisimilis
J. Biol. Chem., February 12, 1999; 274(7): 4239 - 4245.
[Abstract] [Full Text] [PDF]


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J. Physiol.Home page
G A Barker, R J Wilkins, S Golding, and J C Ellory
Neutral amino acid transport in bovine articular chondrocytes
J. Physiol., February 1, 1999; 514(3): 795 - 808.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
D. Torrents, R. Estevez, M. Pineda, E. Fernandez, J. Lloberas, Y.-B. Shi, A. Zorzano, and M. Palacin
Identification and Characterization of a Membrane Protein (y+L Amino Acid Transporter-1) That Associates with 4F2hc to Encode the Amino Acid Transport Activity y+L. A CANDIDATE GENE FOR LYSINURIC PROTEIN INTOLERANCE
J. Biol. Chem., December 4, 1998; 273(49): 32437 - 32445.
[Abstract] [Full Text] [PDF]


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Physiol. Rev.Home page
M. PALACIN, R. ESTEVEZ, J. BERTRAN, and A. ZORZANO
Molecular Biology of Mammalian Plasma Membrane Amino Acid Transporters
Physiol Rev, October 1, 1998; 78(4): 969 - 1054.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
Y. Kanai, Y. Fukasawa, S. H. Cha, H. Segawa, A. Chairoungdua, D. K. Kim, H. Matsuo, J. Y. Kim, K.-i. Miyamoto, E. Takeda, et al.
Transport Properties of a System y+L Neutral and Basic Amino Acid Transporter. INSIGHTS INTO THE MECHANISMS OF SUBSTRATE RECOGNITION
J. Biol. Chem., June 30, 2000; 275(27): 20787 - 20793.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
B. Nicholson, C. K. Manner, J. Kleeman, and C. L. MacLeod
Sustained Nitric Oxide Production in Macrophages Requires the Arginine Transporter CAT2
J. Biol. Chem., May 4, 2001; 276(19): 15881 - 15885.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
D. Llull, E. Garcia, and R. Lopez
Tts, a Processive beta -Glucosyltransferase of Streptococcus pneumoniae, Directs the Synthesis of the Branched Type 37 Capsular Polysaccharide in Pneumococcus and Other Gram-positive Species
J. Biol. Chem., June 8, 2001; 276(24): 21053 - 21061.
[Abstract] [Full Text] [PDF]




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