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Physiol. Rev. 78: 969-1054, 1998;
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PHYSIOLOGICAL REVIEWS   Vol. 78 No. 4 October 1998, pp. 969-1054
Copyright ©1998 The American Physiological Society

Molecular Biology of Mammalian Plasma Membrane Amino Acid Transporters

MANUEL PALACÍN, RAÚL ESTÉVEZ, JOAN BERTRAN, AND ANTONIO ZORZANO

Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, and Departament de Criobiologia i Terapia Cellular, Institut de Recerca Oncològica, Barcelona, Spain

Palacín, Manuel, Raúl Estévez, Joan Bertran, and Antonio Zorzano. Molecular Biology of Mammalian Plasma Membrane Amino Acid Transporters. Physiol. Rev. 78: 969-1054, 1998. --- Molecular biology entered the field of mammalian amino acid transporters in 1990-1991 with the cloning of the first GABA and cationic amino acid transporters. Since then, cDNA have been isolated for more than 20 mammalian amino acid transporters. All of them belong to four protein families. Here we describe the tissue expression, transport characteristics, structure-function relationship, and the putative physiological roles of these transporters. Wherever possible, the ascription of these transporters to known amino acid transport systems is suggested. Significant contributions have been made to the molecular biology of amino acid transport in mammals in the last 3 years, such as the construction of knockouts for the CAT-1 cationic amino acid transporter and the EAAT2 and EAAT3 glutamate transporters, as well as a growing number of studies aimed to elucidate the structure-function relationship of the amino acid transporter. In addition, the first gene (rBAT) responsible for an inherited disease of amino acid transport (cystinuria) has been identified. Identifying the molecular structure of amino acid transport systems of high physiological relevance (e.g., system A, L, N, and x-c) and of the genes responsible for other aminoacidurias as well as revealing the key molecular mechanisms of the amino acid transporters are the main challenges of the future in this field.




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 Am. J. Physiol. Endocrinol. Metab.Home page
R. L. O'Kane and R. A. Hawkins
Na+-dependent transport of large neutral amino acids occurs at the abluminal membrane of the blood-brain barrier
Am J Physiol Endocrinol Metab, December 1, 2003; 285(6): E1167 - E1173.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
J. Burkhalter, H. Fiumelli, I. Allaman, J.-Y. Chatton, and J.-L. Martin
Brain-Derived Neurotrophic Factor Stimulates Energy Metabolism in Developing Cortical Neurons
J. Neurosci., September 10, 2003; 23(23): 8212 - 8220.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
P. F. Speake, J. D. Glazier, P. T.-Y. Ayuk, M. Reade, C. P. Sibley, and S. W. D'Souza
L-Arginine Transport across the Basal Plasma Membrane of the Syncytiotrophoblast of the Human Placenta from Normal and Preeclamptic Pregnancies
J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4287 - 4292.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
V. F. Sacchi, M. Castagna, S. A. Mari, C. Perego, E. Bossi, and A. Peres
Glutamate 59 is critical for transport function of the amino acid cotransporter KAAT1
Am J Physiol Cell Physiol, September 1, 2003; 285(3): C623 - C632.
[Abstract] [Full Text] [PDF]

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 IOVSHome page
B. Jain-Vakkalagadda, S. Dey, D. Pal, and A. K. Mitra
Identification and Functional Characterization of a Na+-Independent Large Neutral Amino Acid Transporter, LAT1, in Human and Rabbit Cornea
Invest. Ophthalmol. Vis. Sci., July 1, 2003; 44(7): 2919 - 2927.
[Abstract] [Full Text] [PDF]

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 J. Nutr.Home page
A. Blais, J.-F. Huneau, L. J. Magrum, T. J. Koehnle, J. W. Sharp, D. Tome, and D. W. Gietzen
Threonine Deprivation Rapidly Activates the System A Amino Acid Transporter in Primary Cultures of Rat Neurons from the Essential Amino Acid Sensor in the Anterior Piriform Cortex
J. Nutr., July 1, 2003; 133(7): 2156 - 2164.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. L. Martinez-Chantar, M. U. Latasa, M. Varela-Rey, S. C. Lu, E. R. Garcia-Trevijano, J. M. Mato, and M. A. Avila
L-Methionine Availability Regulates Expression of the Methionine Adenosyltransferase 2A Gene in Human Hepatocarcinoma Cells: ROLE OF S-ADENOSYLMETHIONINE
J. Biol. Chem., May 23, 2003; 278(22): 19885 - 19890.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
I. Rubio-Aliaga, I. Frey, M. Boll, D. A. Groneberg, H. M. Eichinger, R. Balling, and H. Daniel
Targeted Disruption of the Peptide Transporter Pept2 Gene in Mice Defines Its Physiological Role in the Kidney
Mol. Cell. Biol., May 1, 2003; 23(9): 3247 - 3252.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
H. Daniel and I. Rubio-Aliaga
An update on renal peptide transporters
Am J Physiol Renal Physiol, May 1, 2003; 284(5): F885 - F892.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
H. H. A. G. M. van der Putten, E. C. H. Friesema, N. A. Abumrad, M. E. Everts, and T. J. Visser
Thyroid Hormone Transport by the Rat Fatty Acid Translocase
Endocrinology, April 1, 2003; 144(4): 1315 - 1323.
[Abstract] [Full Text] [PDF]

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 IOVSHome page
H. J. Gukasyan, R. Kannan, V. H. L. Lee, and K.-J. Kim
Regulation of L-Cystine Transport and Intracellular GSH Level by a Nitric Oxide Donor in Primary Cultured Rabbit Conjunctival Epithelial Cell Layers
Invest. Ophthalmol. Vis. Sci., March 1, 2003; 44(3): 1202 - 1210.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
Z. Chen, Y.-J. Fei, C. M H Anderson, K. A Wake, S. Miyauchi, W. Huang, D. T Thwaites, and V. Ganapathy
Structure, function and immunolocalization of a proton-coupled amino acid transporter (hPAT1) in the human intestinal cell line Caco-2
J. Physiol., January 15, 2003; 546(2): 349 - 361.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
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]

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 Physiol. Rev.Home page
G. E. Mann, D. L. Yudilevich, and L. Sobrevia
Regulation of Amino Acid and Glucose Transporters in Endothelial and Smooth Muscle Cells
Physiol Rev, January 1, 2003; 83(1): 183 - 252.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
L. D. Parks and D. W. Barfuss
Transepithelial transport and metabolism of glycine in S1, S2, and S3 cell types of the rabbit proximal tubule
Am J Physiol Renal Physiol, December 1, 2002; 283(6): F1208 - F1215.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
I. Yaman, J. Fernandez, B. Sarkar, R. J. Schneider, M. D. Snider, L. E. Nagy, and M. Hatzoglou
Nutritional Control of mRNA Stability Is Mediated by a Conserved AU-rich Element That Binds the Cytoplasmic Shuttling Protein HuR
J. Biol. Chem., October 25, 2002; 277(44): 41539 - 41546.
[Abstract] [Full Text] [PDF]

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 J. Nutr.Home page
P. J. Bain, R. LeBlanc-Chaffin, H. Chen, S. S. Palii, K. M. Leach, and M. S. Kilberg
The Mechanism for Transcriptional Activation of the Human ATA2 Transporter Gene by Amino Acid Deprivation is Different than That for Asparagine Synthetase
J. Nutr., October 1, 2002; 132(10): 3023 - 3029.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
P. Casanello and L. Sobrevia
Intrauterine Growth Retardation Is Associated With Reduced Activity and Expression of the Cationic Amino Acid Transport Systems y+/hCAT-1 and y+/hCAT-2B and Lower Activity of Nitric Oxide Synthase in Human Umbilical Vein Endothelial Cells
Circ. Res., July 26, 2002; 91(2): 127 - 134.
[Abstract] [Full Text] [PDF]

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 Mol. Biol. CellHome page
A. L. Edinger and C. B. Thompson
Akt Maintains Cell Size and Survival by Increasing mTOR-dependent Nutrient Uptake
Mol. Biol. Cell, July 1, 2002; 13(7): 2276 - 2288.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
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]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
D. M. Shasby
System N in eNdothelium
Am J Physiol Lung Cell Mol Physiol, June 1, 2002; 282(6): L1190 - L1191.
[Full Text] [PDF]

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 J. Physiol.Home page
E. Bossi, S. Giovannardi, F. Binda, G. Forlani, and A. Peres
Role of anion-cation interactions on the pre-steady-state currents of the rat Na+-Cl--dependent GABA cotransporter rGAT1
J. Physiol., June 1, 2002; 541(2): 343 - 350.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
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]

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 JCBHome page
F. A. Chaudhry, R. J. Reimer, and R. H. Edwards
The glutamine commute: take the N line and transfer to the A
J. Cell Biol., April 29, 2002; 157(3): 349 - 355.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
R. Hyde, K. Peyrollier, and H. S. Hundal
Insulin Promotes the Cell Surface Recruitment of the SAT2/ATA2 System A Amino Acid Transporter from an Endosomal Compartment in Skeletal Muscle Cells
J. Biol. Chem., April 12, 2002; 277(16): 13628 - 13634.
[Abstract] [Full Text] [PDF]

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 J. Nutr.Home page
S. Fraga, M. P. Serrao, and P. Soares-da-Silva
L-Type Amino Acid Transporters in Two Intestinal Epithelial Cell Lines Function as Exchangers with Neutral Amino Acids
J. Nutr., April 1, 2002; 132(4): 733 - 738.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
M. Kakoki, W. Wang, and D. L. Mattson
Cationic Amino Acid Transport in the Renal Medulla and Blood Pressure Regulation
Hypertension, February 1, 2002; 39(2): 287 - 292.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
F. A. Chaudhry, D. Schmitz, R. J. Reimer, P. Larsson, A. T. Gray, R. Nicoll, M. Kavanaugh, and R. H. Edwards
Glutamine Uptake by Neurons: Interaction of Protons with System A Transporters
J. Neurosci., January 1, 2002; 22(1): 62 - 72.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
R. Sala, B. M. Rotoli, E. Colla, R. Visigalli, A. Parolari, O. Bussolati, G. C. Gazzola, and V. Dall'Asta
Two-way arginine transport in human endothelial cells: TNF-alpha stimulation is restricted to system y+
Am J Physiol Cell Physiol, January 1, 2002; 282(1): C134 - C143.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
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]

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 EndocrinologyHome page
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]

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 Am. J. Physiol. Cell Physiol.Home page
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]

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 Cardiovasc ResHome page
N. King, H. Williams, J. D McGivan, and M.-S. Suleiman
Characteristics of L-aspartate transport and expression of EAAC-1 in sarcolemmal vesicles and isolated cells from rat heart
Cardiovasc Res, October 1, 2001; 52(1): 84 - 94.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
N. E. Avissar, C. K. Ryan, V. Ganapathy, and H. C. Sax
Na+-dependent neutral amino acid transporter ATB0 is a rabbit epithelial cell brush-border protein
Am J Physiol Cell Physiol, September 1, 2001; 281(3): C963 - C971.
[Abstract] [Full Text] [PDF]

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

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Ugawa, Y. Sunouchi, T. Ueda, E. Takahashi, Y. Saishin, and S. Shimada
Characterization of a mouse colonic system B0+ amino acid transporter related to amino acid absorption in colon
Am J Physiol Gastrointest Liver Physiol, August 1, 2001; 281(2): G365 - G370.
[Abstract] [Full Text] [PDF]


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