Molecular Biology of Mammalian Plasma Membrane Amino Acid Transporters

1998 ◽  
Vol 78 (4) ◽  
pp. 969-1054 ◽  
Author(s):  
MANUEL PALACÍN ◽  
RAÚL ESTÉVEZ ◽  
JOAN BERTRAN ◽  
ANTONIO ZORZANO
Keyword(s):  
Plasma Membrane ◽  
Amino Acid ◽  
Molecular Biology ◽  
Structure Function ◽  
Amino Acid Transport ◽  
Transport Systems ◽  
Amino Acid Transporters ◽  
Acid Transport ◽  
Cationic Amino Acid ◽  
Function Relationship

Palacı́n, 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.

Placental amino acid transport

1995 ◽  
Vol 268 (6) ◽  
pp. C1321-C1331 ◽  
Author(s):  
A. J. Moe
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Human Placenta ◽  
Amino Acid Transport ◽  
Single Layer ◽  
Maternal Blood ◽  
Transport Systems ◽  
Amino Acid Transporters ◽  
Acid Transport ◽  
Principal Mechanism

Normal fetal growth and development depend on a continuous supply of amino acids from the mother to the fetus. The placenta is responsible for the transfer of amino acids between the two circulations. The human placenta is hemomonochorial, meaning that the maternal and fetal circulations are separated by a single layer of polarized epithelium called the syncytiotrophoblast, which is in direct contact with maternal blood. Transport proteins located in the microvillous and basal membranes of the syncytiotrophoblast are the principal mechanism for transfer from maternal blood to fetal blood. Knowledge of the function and regulation of syncytiotrophoblast amino acid transporters is of great importance in understanding the mechanism of placental transport and potentially improving fetal and newborn outcomes. The development of methods for the isolation of microvillous and basal membrane vesicles from human placenta over the past two decades has contributed greatly to this understanding. Now a primary cultured trophoblast model is available to study amino acid transport and regulation as the cells differentiate. The types of amino acid transporters and their distribution between the syncytiotrophoblast microvillous and basal membranes are somewhat unique compared with other polarized epithelia. These differences may reflect the unusual circumstance of this epithelium that is exposed to blood on both sides. The current state of knowledge as to the types of transport systems present in syncytiotrophoblast, their regulation, and the effects of maternal consumption of drugs on transport are discussed.

Multiple pathways for cationic amino acid transport in rat thyroid epithelial cell line PC Cl3

2005 ◽  
Vol 288 (2) ◽  
pp. C290-C303 ◽  
Author(s):  
Tiziano Verri ◽  
Cinzia Dimitri ◽  
Sonia Treglia ◽  
Fabio Storelli ◽  
Stefania De Micheli ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cell Line ◽  
Amino Acid Transport ◽  
Transport Systems ◽  
Residual Fraction ◽  
Acid Transport ◽  
Thyroid Cells ◽  
Cationic Amino Acid ◽  
Rat Thyroid

Information regarding cationic amino acid transport systems in thyroid is limited to Northern blot detection of y+LAT1 mRNA in the mouse. This study investigated cationic amino acid transport in PC cell line clone 3 (PC Cl3 cells), a thyroid follicular cell line derived from a normal Fisher rat retaining many features of normal differentiated follicular thyroid cells. We provide evidence that in PC Cl3 cells plasmalemmal transport of cationic amino acids is Na+ independent and occurs, besides diffusion, with the contribution of high-affinity, carrier-mediated processes. Carrier-mediated transport is via y+, y+L, and b0,+ systems, as assessed by l-arginine uptake and kinetics, inhibition of l-arginine transport by N-ethylmaleimide and neutral amino acids, and l-cystine transport studies. y+L and y+ systems account for the highest transport rate (with y+L > y+) and b0,+ for a residual fraction of the transport. Uptake data correlate to expression of the genes encoding for CAT-1, CAT-2B, 4F2hc, y+LAT1, y+LAT2, rBAT, and b0,+AT, an expression profile that is also shown by the rat thyroid gland. In PC Cl3 cells cationic amino acid uptake is under TSH and/or cAMP control (with transport increasing with increasing TSH concentration), and upregulation of CAT-1, CAT-2B, 4F2hc/y+LAT1, and rBAT/b0,+AT occurs at the mRNA level under TSH stimulation. Our results provide the first description of an expression pattern of cationic amino acid transport systems in thyroid cells. Furthermore, we provide evidence that extracellular l-arginine is a crucial requirement for normal PC Cl3 cell growth and that long-term l-arginine deprivation negatively influences CAT-2B expression, as it correlates to reduction of CAT-2B mRNA levels.

scholarly journals Expression of solute carrier 7A4 (SLC7A4) in the plasma membrane is not sufficient to mediate amino acid transport activity

2002 ◽  
Vol 364 (3) ◽  
pp. 767-775 ◽  
Author(s):  
Sabine WOLF ◽  
Annette JANZEN ◽  
Nicole VÉKONY ◽  
Ursula MARTINÉ ◽  
Dennis STRAND ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Amino Acid ◽  
Protein Expression ◽  
Amino Acid Transport ◽  
Fluorescent Protein ◽  
Xenopus Laevis Oocytes ◽  
Amino Acid Transporters ◽  
Acid Transport ◽  
Transport Activity ◽  
Solute Carrier

Member 4 of human solute carrier family 7 (SLC7A4) exhibits significant sequence homology with the SLC7 subfamily of human cationic amino acid transporters (hCATs) [Sperandeo, Borsani, Incerti, Zollo, Rossi, Zuffardi, Castaldo, Taglialatela, Andria and Sebastio (1998) Genomics 49, 230–236]. It is therefore often referred to as hCAT-4 even though no convincing transport activity has been shown for this protein. We expressed SLC7A4 in Xenopus laevis oocytes, but could not detect any transport activity for cationic, neutral or anionic amino acids or for the polyamine putrescine. In addition, human glioblastoma cells stably overexpressing a fusion protein between SLC7A4 and the enhanced green fluorescent protein (EGFP) did not exhibit an increased transport activity for l-arginine. The lack of transport activity was not due to a lack of SLC7A4 protein expression in the plasma membrane, as in both cell types SLC7A4-EGFP exhibited a similar subcellular localization and level of protein expression as functional hCAT-EGFP proteins. The expression of SLC7A4 can be induced in NT2 teratocarcinoma cells by treatment with retinoic acid. However, also for this endogenously expressed SLC7A4, we could not detect any transport activity for l-arginine. Our data demonstrate that the expression of SLC7A4 in the plasma membrane is not sufficient to induce an amino acid transport activity in X. laevis oocytes or human cells. Therefore, SLC7A4 is either not an amino acid transporter or it needs additional (protein) factor(s) to be functional.

Heteromeric amino acid transporters: biochemistry, genetics, and physiology

2001 ◽  
Vol 281 (6) ◽  
pp. F995-F1018 ◽  
Author(s):  
Josep Chillarón ◽  
Ramón Roca ◽  
Alfonso Valencia ◽  
Antonio Zorzano ◽  
Manuel Palacín
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Human Genetics ◽  
Disulfide Bridge ◽  
Transport Systems ◽  
Cell Physiology ◽  
Amino Acid Transporters ◽  
Acid Transport ◽  
Membrane Glycoproteins ◽  
Cell Functions

The heteromeric amino acid transporters (HATs) are composed of two polypeptides: a heavy subunit (HSHAT) and a light subunit (LSHAT) linked by a disulfide bridge. HSHATs are N-glycosylated type II membrane glycoproteins, whereas LSHATs are nonglycosylated polytopic membrane proteins. The HSHATs have been known since 1992, and the LSHATs have been described in the last three years. HATs represent several of the classic mammalian amino acid transport systems (e.g., L isoforms, y+L isoforms, asc, x[Formula: see text], and b0,+). Members of the HAT family are the molecular bases of inherited primary aminoacidurias cystinuria and lysinuric protein intolerance. In addition to the role in amino acid transport, one HSHAT [the heavy subunit of the cell-surface antigen 4F2 (also named CD98)] is involved in other cell functions that might be related to integrin activation. This review covers the biochemistry, human genetics, and cell physiology of HATs, including the multifunctional character of CD98.

scholarly journals Gene-product designations for amino acid transporters.

1994 ◽  
Vol 196 (1) ◽  
pp. 51-57 ◽  
Author(s):  
H N Christensen ◽  
L M Albritton ◽  
D K Kakuda ◽  
C L MacLeod
Keyword(s):  
Amino Acid ◽  
Gene Product ◽  
Amino Acid Transport ◽  
Full Range ◽  
Transport Systems ◽  
Amino Acid Transporters ◽  
Gene Products ◽  
Acid Transport ◽  
Good Set ◽  
Cloned Gene

The molecular cloning of genes that encode amino acid transporters presents the scientific community with the opportunity to name their gene products using a scheme that could usefully recall the well-defined transport system most similar in properties to the newly identified cloned gene product. To avoid the problem of rising confusion, we propose to take advantage of established designation methods that indicate the types of amino acids transported and the co-substrate ion requirement of their transport. The economy obligated by the necessity to keep the number of symbols in a gene name to a minimum will rarely permit a listing of the full range of substrates, since amino acid transport systems have broad substrate specificities with co-substrate requirements that can differ in a substrate-specific manner. Hence, the use of established systems to codify groups of amino acid transport systems, which allow identification of the substrate range by using 1-3 letters, e.g. A, L or even ASC, could be integrated with a system used to indicate the ion-dependence of transport. The discoverers of transporters are mainly proceeding with commendable reserve and are inviting discussion, a desire which this essay urges be facilitated by more formal arrangements for further planning. These discoverers have also shown, along with an expressed desire for guidance, well-advised spontaneity in making reference to the substrate range, two trends that together suggest that a good set of designations can evolve that will be highly descriptive.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Arginine Homeostasis in J774.1 Macrophages in the Context of Mycobacterium bovis BCG Infection

2006 ◽  
Vol 188 (13) ◽  
pp. 4830-4840 ◽  
Author(s):  
Meliza T. Talaue ◽  
Vishwanath Venketaraman ◽  
Manzour Hernando Hazbón ◽  
Marcy Peteroy-Kelly ◽  
Anjali Seth ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mycobacterium Bovis ◽  
Amino Acid Transport ◽  
Host Cells ◽  
Transport Systems ◽  
Acid Transport ◽  
Intracellular Growth ◽  
Cationic Amino Acid ◽  
Arginine Transport ◽  
Arginine Uptake

ABSTRACT The competition for l-arginine between the inducible nitric oxide synthase and arginase contributes to the outcome of several parasitic and bacterial infections. The acquisition of l-arginine, however, is important not only for the host cells but also for the intracellular pathogen. In this study we observe that strain AS-1, the Mycobacterium bovis BCG strain lacking the Rv0522 gene, which encodes an arginine permease, perturbs l-arginine metabolism in J774.1 murine macrophages. Infection with AS-1, but not with wild-type BCG, induced l-arginine uptake in J774.1 cells. This increase in l-arginine uptake was independent of activation with gamma interferon plus lipopolysaccharide and correlated with increased expression of the MCAT1 and MCAT2 cationic amino acid transport genes. AS-1 infection also enhanced arginase activity in resting J774.1 cells. Survival studies revealed that AS-1 survived better than BCG within resting J774.1 cells. Intracellular growth of AS-1 was further enhanced by inhibiting arginase and ornithine decarboxylase activities in J774.1 cells using l-norvaline and difluoromethylornithine treatment, respectively. These results suggest that the arginine-related activities of J774.1 macrophages are affected by the arginine transport capacity of the infecting BCG strain. The loss of Rv0522 gene-encoded arginine transport may have induced other cationic amino acid transport systems during intracellular growth of AS-1, allowing better survival within resting macrophages.

Ontogeny of cationic amino acid transport systems in rat placenta

1994 ◽  
Vol 267 (3) ◽  
pp. C804-C811 ◽  
Author(s):  
M. S. Malandro ◽  
M. J. Beveridge ◽  
M. S. Kilberg ◽  
D. A. Novak
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Placental Transfer ◽  
Basal Membrane ◽  
Membrane System ◽  
Transport Systems ◽  
Northern Analysis ◽  
Membrane Domains ◽  
Acid Transport ◽  
Cationic Amino Acid

Gestational regulation of the placental transfer of amino acids from maternal to fetal circulations is essential for the proper development of the fetus. The cationic amino acid transport systems of the microvillous (maternal facing) and basal (fetal facing) membranes of the rat placental syncytiotrophoblast were examined. Inhibition analysis documented the presence of three kinetically distinct cationic amino acid transport mechanisms: a single Na(+)-dependent mechanism in the microvillous membrane, which increased in activity from 14 to 20 days gestation but was absent from the basal membrane throughout the entire gestational period (system Bo,+), and two Na(+)-independent transport systems in both membrane domains, one that is completely inhibited by leucine, which increased in activity in both the microvillous and basal membrane domains, and the other that is leucine insensitive, which remained fairly constant in the basal membrane and increased throughout gestation in the microvillous membrane (system y1+). Northern analysis with the system y1+ cDNA revealed a specific band of approximately 7.4-7.9 kb, which increased with increasing gestational age.

scholarly journals Amino acid transport systems of lysosomes: Possible substitute utility of a surviving transport system for one congenitally defective or absent

1988 ◽  
Vol 8 (2) ◽  
pp. 121-129 ◽  
Author(s):  
Halvor N. Christensen
Keyword(s):  
Plasma Membrane ◽  
Amino Acid ◽  
Transport System ◽  
Amino Acid Transport ◽  
Transport Systems ◽  
Acid Transport

Ways in which other transport systems may compensate for one that is genetically defective are considered. Comparisons of the transport systems of organelles (here the lysosome) with the transport system at the plasma membrane has significant implications for chemotherapy.

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