| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
(Received for publication, November 28, 1995, and in revised form, February 26, 1996)
From the Department of Pharmacology and Toxicology, Kyorin
University School of Medicine, 6-20-2 Shinkawa, Mitaka,
Tokyo 181, Japan
A cDNA was isolated from mouse testis which
encodes a Na+-dependent neutral amino acid
transporter. The encoded protein, designated ASCT2, showed amino acid
sequence similarity to the mammalian glutamate transporters (40-44%
identity), Na+-dependent neutral amino acid
transporter ASCT1 (57% identity; Arriza, J. L., Kavanaugh, M. P.,
Fairman, W. A., Wu, Y.-N., Murdoch, G. H., North, R. A., and Amara, S. G. (1993) J. Biol. Chem. 268, 15329-15332; Shafqat, S.,
Tamarappoo, B. K., Kilberg, M. S., Puranam, R. S., McNamara, J. O.,
Guadano-Ferraz, A., and Fremeau, T., Jr. (1993) J. Biol.
Chem. 268, 15351-15355) and a mouse adipocyte
differentiation-associated gene product AAAT (94% identity; Liao, K.,
and Lane, D. (1995) Biochem. Biophys. Res. Commun. 208, 1008-1015). When expressed in Xenopus laevis oocytes,
ASCT2 exhibited Na+-dependent uptakes of
neutral amino acids such as L-alanine,
L-serine, L-threonine, L-cysteine,
and L-glutamine at high affinity with
Km values around 20 µM.
L-Methionine, L-leucine, L-glycine,
and L-valine were also transported by ASCT2 but with lower
affinity. The substrate selectivity of ASCT2 was typical of amino acid
transport system ASC, which prefers neutral amino acids without bulky
or branched side chains. ASCT2 also transported L-glutamate
at low affinity (Km = 1.6 mM).
L-Glutamate transport was enhanced by lowering
extracellular pH, suggesting that L-glutamate was
transported as protonated form. In contrast to electrogenic transport
of glutamate transporters and the other ASC isoform ASCT1,
ASCT2-mediated amino acid transport was electroneutral. Na+
dependence of L-alanine uptake fits to the Michaelis-Menten
equation, suggesting a single Na+ cotransported with one
amino acid, which was distinct from glutamate transporters coupled to
two Na+. Northern blot hybridization revealed that ASCT2
was mainly expressed in kidney, large intestine, lung, skeletal muscle,
testis, and adipose tissue. Functional characterization of ASCT2
provided fruitful information on the properties of substrate binding
sites and the mechanisms of transport of
Na+-dependent neutral and acidic amino acid
transporter family, which would facilitate the structure-function
analyses based on the comparison of the primary structures of ASCT2 and
the other members of the family.
Volume 271, Number 25,
Issue of June 21, 1996
pp. 14883-14890
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Broer Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia Physiol Rev, January 1, 2008; 88(1): 249 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Pinho, V. Pinto, M. P. Serrao, P. A. Jose, and P. Soares-da-Silva Underexpression of the Na+-dependent neutral amino acid transporter ASCT2 in the spontaneously hypertensive rat kidney Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R538 - R547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Pinho, M. P. Serrao, and P. Soares-da-Silva High-salt intake and the renal expression of amino acid transporters in spontaneously hypertensive rats Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1452 - F1463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Li, J. Lim, M. D. Jacobs, J. Kistler, and P. J. Donaldson Regional Differences in Cystine Accumulation Point to a Sutural Delivery Pathway to the Lens Core Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1253 - 1260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fukuhara, Y. Kanai, A. Chairoungdua, E. Babu, F. Bessho, T. Kawano, Y. Akimoto, H. Endou, and K. Yan Protein Characterization of Na+-Independent System L Amino Acid Transporter 3 in Mice: A Potential Role in Supply of Branched-Chain Amino Acids under Nutrient Starvation Am. J. Pathol., March 1, 2007; 170(3): 888 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. H. Leighton, R. P. Seal, S. D. Watts, M. O. Skyba, and S. G. Amara Structural Rearrangements at the Translocation Pore of the Human Glutamate Transporter, EAAT1 J. Biol. Chem., October 6, 2006; 281(40): 29788 - 29796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Tao, Z. Zhang, and C. Grewer Neutralization of the Aspartic Acid Residue Asp-367, but Not Asp-454, Inhibits Binding of Na+ to the Glutamate-free Form and Cycling of the Glutamate Transporter EAAC1 J. Biol. Chem., April 14, 2006; 281(15): 10263 - 10272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hosoi, K. Takeuchi, H. Sawada, and H. Toyohara Expression and functional analysis of mussel taurine transporter, as a key molecule in cellular osmoconforming J. Exp. Biol., November 15, 2005; 208(22): 4203 - 4211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lim, Y. C. Lam, J. Kistler, and P. J. Donaldson Molecular Characterization of the Cystine/Glutamate Exchanger and the Excitatory Amino Acid Transporters in the Rat Lens Invest. Ophthalmol. Vis. Sci., August 1, 2005; 46(8): 2869 - 2877. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Xu and M. E. Hemler Metabolic Activation-related CD147-CD98 Complex Mol. Cell. Proteomics, August 1, 2005; 4(8): 1061 - 1071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Palacin, V. Nunes, M. Font-Llitjos, M. Jimenez-Vidal, J. Fort, E. Gasol, M. Pineda, L. Feliubadalo, J. Chillaron, and A. Zorzano The Genetics of Heteromeric Amino Acid Transporters Physiology, April 1, 2005; 20(2): 112 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Takanaga, B. Mackenzie, Y. Suzuki, and M. A. Hediger Identification of Mammalian Proline Transporter SIT1 (SLC6A20) with Characteristics of Classical System Imino J. Biol. Chem., March 11, 2005; 280(10): 8974 - 8984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. E. Avissar, T. R. Ziegler, L. Toia, L. Gu, E. C. Ray, J. Berlanga-Acosta, and H. C. Sax ATB0/ASCT2 Expression in Residual Rabbit Bowel Is Decreased after Massive Enterectomy and Is Restored by Growth Hormone Treatment J. Nutr., September 1, 2004; 134(9): 2173 - 2177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Grewer and E. Grabsch New inhibitors for the neutral amino acid transporter ASCT2 reveal its Na+-dependent anion leak J. Physiol., June 15, 2004; 557(3): 747 - 759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Broer, K. Klingel, S. Kowalczuk, J. E. J. Rasko, J. Cavanaugh, and S. Broer Molecular Cloning of Mouse Amino Acid Transport System B0, a Neutral Amino Acid Transporter Related to Hartnup Disorder J. Biol. Chem., June 4, 2004; 279(23): 24467 - 24476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Babu, Y. Kanai, A. Chairoungdua, D. K. Kim, Y. Iribe, S. Tangtrongsup, P. Jutabha, Y. Li, N. Ahmed, S. Sakamoto, et al. Identification of a Novel System L Amino Acid Transporter Structurally Distinct from Heterodimeric Amino Acid Transporters J. Biol. Chem., October 31, 2003; 278(44): 43838 - 43845. [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]
|
|
|
|
|
|
A. Umesh, B. N. Cohen, L. S. Ross, and S. S. Gill Functional characterization of a glutamate/aspartate transporter from the mosquito Aedes aegypti J. Exp. Biol., July 1, 2003; 206(13): 2241 - 2255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Marin, D. Lavillette, S. M. Kelly, and D. Kabat N-Linked Glycosylation and Sequence Changes in a Critical Negative Control Region of the ASCT1 and ASCT2 Neutral Amino Acid Transporters Determine Their Retroviral Receptor Functions J. Virol., March 1, 2003; 77(5): 2936 - 2945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Grewer, N. Watzke, T. Rauen, and A. Bicho Is the Glutamate Residue Glu-373 the Proton Acceptor of the Excitatory Amino Acid Carrier 1? J. Biol. Chem., January 17, 2003; 278(4): 2585 - 2592. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sakai, H. Shimizu, T. Koike, S. Furuya, and M. Watanabe Neutral Amino Acid Transporter ASCT1 Is Preferentially Expressed in L-Ser-Synthetic/Storing Glial Cells in the Mouse Brain with Transient Expression in Developing Capillaries J. Neurosci., January 15, 2003; 23(2): 550 - 560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
A. M. Karinch, C.-M. Lin, C. L. Wolfgang, M. Pan, and W. W. Souba Regulation of expression of the SN1 transporter during renal adaptation to chronic metabolic acidosis in rats Am J Physiol Renal Physiol, November 1, 2002; 283(5): F1011 - F1019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. P. Bode, B. C. Fuchs, B. P. Hurley, J. L. Conroy, J. E. Suetterlin, K. K. Tanabe, D. B. Rhoads, S. F. Abcouwer, and W. W. Souba Molecular and functional analysis of glutamine uptake in human hepatoma and liver-derived cells Am J Physiol Gastrointest Liver Physiol, November 1, 2002; 283(5): G1062 - G1073. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Lavillette, M. Marin, A. Ruggieri, F. Mallet, F.-L. Cosset, and D. Kabat The Envelope Glycoprotein of Human Endogenous Retrovirus Type W Uses a Divergent Family of Amino Acid Transporters/Cell Surface Receptors J. Virol., June 5, 2002; 76(13): 6442 - 6452. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 H. Uchino, Y. Kanai, D. K. Kim, M. F. Wempe, A. Chairoungdua, E. Morimoto, M. W. Anders, and H. Endou Transport of Amino Acid-Related Compounds Mediated by L-Type Amino Acid Transporter 1 (LAT1): Insights Into the Mechanisms of Substrate Recognition Mol. Pharmacol., April 1, 2002; 61(4): 729 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Smith, V. Haroutunian, K. L. Davis, and J. H. Meador-Woodruff Expression of Excitatory Amino Acid Transporter Transcripts in the Thalamus of Subjects With Schizophrenia Am J Psychiatry, September 1, 2001; 158(9): 1393 - 1399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
B. P. Bode Recent Molecular Advances in Mammalian Glutamine Transport J. Nutr., September 1, 2001; 131(9): 2475S - 2485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
T. Welbourne and I. Nissim Regulation of mitochondrial glutamine/glutamate metabolism by glutamate transport: studies with 15N Am J Physiol Cell Physiol, May 1, 2001; 280(5): C1151 - C1159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Jean, S. Rome, V. Mathé, J.-F. Huneau, N. Aattouri, G. Fromentin, C. L. Achagiotis, and D. Tomé Metabolic Evidence for Adaptation to a High Protein Diet in Rats J. Nutr., January 1, 2001; 131(1): 91 - 98. [Abstract] [Full Text]
|
|
|
|
|
|
M. Marin, C. S. Tailor, A. Nouri, and D. Kabat Sodium-Dependent Neutral Amino Acid Transporter Type 1 Is an Auxiliary Receptor for Baboon Endogenous Retrovirus J. Virol., September 1, 2000; 74(17): 8085 - 8093. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. J. Reimer, F. A. Chaudhry, A. T. Gray, and R. H. Edwards Amino acid transport System A resembles System N in sequence but differs in mechanism PNAS, June 14, 2000; (2000) 140152797. [Abstract] [Full Text]
|
|
|
|
|
|
M. Grunewald and B. I. Kanner The Accessibility of a Novel Reentrant Loop of the Glutamate Transporter GLT-1 Is Restricted by Its Substrate J. Biol. Chem., March 24, 2000; 275(13): 9684 - 9689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Fukasawa, H. Segawa, J. Y. Kim, A. Chairoungdua, D. K. Kim, H. Matsuo, S. H. Cha, H. Endou, and Y. Kanai Identification and Characterization of a Na+-independent Neutral Amino Acid Transporter That Associates with the 4F2 Heavy Chain and Exhibits Substrate Selectivity for Small Neutral D- and L-Amino Acids J. Biol. Chem., March 24, 2000; 275(13): 9690 - 9698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Varoqui, H. Zhu, D. Yao, H. Ming, and J. D. Erickson Cloning and Functional Identification of a Neuronal Glutamine Transporter J. Biol. Chem., February 11, 2000; 275(6): 4049 - 4054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chairoungdua, H. Segawa, J. Y. Kim, K.-i. Miyamoto, H. Haga, Y. Fukui, K.'i. Mizoguchi, H. Ito, E. Takeda, H. Endou, et al. Identification of an Amino Acid Transporter Associated with the Cystinuria-related Type II Membrane Glycoprotein J. Biol. Chem., October 8, 1999; 274(41): 28845 - 28848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Hediger Glutamate transporters in kidney and brain Am J Physiol Renal Physiol, October 1, 1999; 277(4): F487 - F492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Masson, C. Sagne, M. Hamon, and S. E. Mestikawy Neurotransmitter Transporters in the Central Nervous System Pharmacol. Rev., September 1, 1999; 51(3): 439 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Segawa, Y. Fukasawa, K.-i. Miyamoto, E. Takeda, H. Endou, and Y. Kanai Identification and Functional Characterization of a Na+-independent Neutral Amino Acid Transporter with Broad Substrate Selectivity J. Biol. Chem., July 9, 1999; 274(28): 19745 - 19751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Slotboom, W. N. Konings, and J. S. Lolkema Structural Features of the Glutamate Transporter Family Microbiol. Mol. Biol. Rev., June 1, 1999; 63(2): 293 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Silbernagl, K. Volker, and W. H. Dantzler D-Serine is reabsorbed in rat renal pars recta Am J Physiol Renal Physiol, June 1, 1999; 276(6): F857 - F863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. J. Rasko, J.-L. Battini, R. J. Gottschalk, I. Mazo, and A. D. Miller The RD114/simian type D retrovirus receptor is a neutral amino acid transporter PNAS, March 2, 1999; 96(5): 2129 - 2134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Lohmann, W. W. Souba, and B. P. Bode Rat liver endothelial cell glutamine transporter and glutaminase expression contrast with parenchymal cells Am J Physiol Gastrointest Liver Physiol, March 1, 1999; 276(3): G743 - G750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang and B. I. Kanner Two serine residues of the glutamate transporter GLT-1 are crucial for coupling the fluxes of sodium and the neurotransmitter PNAS, February 16, 1999; 96(4): 1710 - 1715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Munck and L. K. Munck Effects of pH changes on systems ASC and B in rabbit ileum Am J Physiol Gastrointest Liver Physiol, January 1, 1999; 276(1): G173 - G184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Ogawa, Y.-M. Kim, T. Mizushima, and T. Tsuchiya Cloning and Expression of the Gene for the Na+-Coupled Serine Transporter from Escherichia coli and Characteristics of the Transporter J. Bacteriol., December 15, 1998; 180(24): 6749 - 6752. [Abstract] [Full Text]
|
|
|
|
|
|
W. Danysz and C. G. Parsons Glycine and N-Methyl-D-Aspartate Receptors: Physiological Significance and Possible Therapeutic Applications Pharmacol. Rev., December 1, 1998; 50(4): 597 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
Y. Kanai, H. Segawa, K.-i. Miyamoto, H. Uchino, E. Takeda, and H. Endou Expression Cloning and Characterization of a Transporter for Large Neutral Amino Acids Activated by the Heavy Chain of 4F2 Antigen (CD98) J. Biol. Chem., September 11, 1998; 273(37): 23629 - 23632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Boorer and W.-N. Fischer Specificity and Stoichiometry of the Arabidopsis H+/Amino Acid Transporter AAP5 J. Biol. Chem., May 16, 1997; 272(20): 13040 - 13046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Zerangue and M. P. Kavanaugh ASCT-1 Is a Neutral Amino Acid Exchanger with Chloride Channel Activity J. Biol. Chem., November 8, 1996; 271(45): 27991 - 27994. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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., |
