amino acid transport systems

Summary

Summary: Cellular proteins and protein complexes that transport amino acids across biological membranes.

Top Publications

  1. Pillai S, Meredith D. SLC36A4 (hPAT4) is a high affinity amino acid transporter when expressed in Xenopus laevis oocytes. J Biol Chem. 2011;286:2455-60 pubmed publisher
  2. Price D, Duncan R, Shigenobu S, Wilson A. Genome expansion and differential expression of amino acid transporters at the aphid/Buchnera symbiotic interface. Mol Biol Evol. 2011;28:3113-26 pubmed publisher
  3. Merhi A, Andre B. Internal amino acids promote Gap1 permease ubiquitylation via TORC1/Npr1/14-3-3-dependent control of the Bul arrestin-like adaptors. Mol Cell Biol. 2012;32:4510-22 pubmed publisher
  4. Dündar E, Bush D. BAT1, a bidirectional amino acid transporter in Arabidopsis. Planta. 2009;229:1047-56 pubmed publisher
    ..A transposon--GUS gene-trap insert in the BAT1 gene displays GUS localization in the vascular tissues (Dundar in Ann Appl Biol, 2009) suggesting BAT1 may function in amino acid export from the phloem into sink tissues. ..
  5. Roos S, Lagerlöf O, Wennergren M, Powell T, Jansson T. Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mTOR signaling. Am J Physiol Cell Physiol. 2009;297:C723-31 pubmed publisher
    ..We conclude that the mTOR pathway represents an important intracellular regulatory link between nutrient and growth factor concentrations and amino acid transport in the human placenta. ..
  6. Shaffer P, Goehring A, Shankaranarayanan A, Gouaux E. Structure and mechanism of a Na+-independent amino acid transporter. Science. 2009;325:1010-4 pubmed publisher
    ..We propose that lysine-158 is central to proton-coupled transport and that the amine group serves the same functional role as the Na2 ion in LeuT, thus demonstrating common principles among proton- and sodium-coupled transporters. ..
  7. Goberdhan D, Ogmundsdóttir M, Kazi S, Reynolds B, Visvalingam S, Wilson C, et al. Amino acid sensing and mTOR regulation: inside or out?. Biochem Soc Trans. 2009;37:248-52 pubmed publisher
    ..The present review summarizes current ideas and suggests ways in which some of the models proposed might be unified to produce an amino acid detection system that can adapt to environmental change. ..
  8. Gao X, Zhou L, Jiao X, Lu F, Yan C, Zeng X, et al. Mechanism of substrate recognition and transport by an amino acid antiporter. Nature. 2010;463:828-32 pubmed publisher
    ..Structural analysis identified three potential gates, involving four aromatic residues and Glu 208, which may work in concert to differentially regulate the upload and release of Arg and Agm. ..
  9. Lolkema J, Slotboom D. The major amino acid transporter superfamily has a similar core structure as Na+-galactose and Na+-leucine transporters. Mol Membr Biol. 2008;25:567-70 pubmed publisher
    ..The APC superfamily contains the major amino acid transporter families that are found throughout life. Insight into their structure will significantly facilitate the studies of this important group of transporters. ..

Scientific Experts

More Information

Publications62

  1. Roos S, Kanai Y, Prasad P, Powell T, Jansson T. Regulation of placental amino acid transporter activity by mammalian target of rapamycin. Am J Physiol Cell Physiol. 2009;296:C142-50 pubmed publisher
    ..These data suggest that mTOR regulates placental amino acid transporters by posttranslational modifications or by affecting transporter translocation to the plasma membrane. ..
  2. Weigelt K, Küster H, Radchuk R, Muller M, Weichert H, Fait A, et al. Increasing amino acid supply in pea embryos reveals specific interactions of N and C metabolism, and highlights the importance of mitochondrial metabolism. Plant J. 2008;55:909-26 pubmed publisher
    ..These results demonstrate that legume seeds have a high capacity to regulate N:C ratios, and highlight the importance of mitochondria in the control of N-C balance and amino acid homeostasis. ..
  3. Ishizuka Y, Kakiya N, Nawa H, Takei N. Leucine induces phosphorylation and activation of p70S6K in cortical neurons via the system L amino acid transporter. J Neurochem. 2008;106:934-42 pubmed publisher
    ..We propose that leucine plays important roles in regulating signaling by p70S6 kinase by acting as an intercellular communicator in the CNS. ..
  4. Gresham D, Usaite R, Germann S, Lisby M, Botstein D, Regenberg B. Adaptation to diverse nitrogen-limited environments by deletion or extrachromosomal element formation of the GAP1 locus. Proc Natl Acad Sci U S A. 2010;107:18551-6 pubmed publisher
    ..We propose that this genomic architecture facilitates evolvability of S. cerevisiae populations exposed to variation in levels and sources of environmental nitrogen. ..
  5. Heublein S, Kazi S, Ogmundsdóttir M, Attwood E, Kala S, Boyd C, et al. Proton-assisted amino-acid transporters are conserved regulators of proliferation and amino-acid-dependent mTORC1 activation. Oncogene. 2010;29:4068-79 pubmed publisher
    ..Therefore our data are consistent with a model in which PATs modulate the activity of mTORC1 not by transporting amino acids into the cell but by modulating the intracellular response to amino acids. ..
  6. Grillo M, Lanza A, Colombatto S. Transport of amino acids through the placenta and their role. Amino Acids. 2008;34:517-23 pubmed publisher
    ..This occurs for instance for arginine, which gives rise to polyamines and to NO. Interconversion occurs among few other amino acids Transport is altered in pregnancy complications, such as restricted fetal growth. ..
  7. Kryndushkin D, Shewmaker F, Wickner R. Curing of the [URE3] prion by Btn2p, a Batten disease-related protein. EMBO J. 2008;27:2725-35 pubmed publisher
    ..Btn2p curing requires cell division, and our results suggest that Btn2p is part of a system, reminiscent of the mammalian aggresome, that collects aggregates preventing their efficient distribution to progeny cells. ..
  8. Rosario F, Jansson N, Kanai Y, Prasad P, Powell T, Jansson T. Maternal protein restriction in the rat inhibits placental insulin, mTOR, and STAT3 signaling and down-regulates placental amino acid transporters. Endocrinology. 2011;152:1119-29 pubmed publisher
    ..We speculate that maternal endocrine and metabolic control of placental nutrient transport reduces fetal growth in response to protein restriction. ..
  9. MacGurn J, Hsu P, Smolka M, Emr S. TORC1 regulates endocytosis via Npr1-mediated phosphoinhibition of a ubiquitin ligase adaptor. Cell. 2011;147:1104-17 pubmed publisher
  10. Couturier J, De Fay E, Fitz M, Wipf D, Blaudez D, Chalot M. PtAAP11, a high affinity amino acid transporter specifically expressed in differentiating xylem cells of poplar. J Exp Bot. 2010;61:1671-82 pubmed publisher
    ..The present study provides important information highlighting the role of a specific amino acid transporter in xylogenesis in poplar. ..
  11. Rentsch D, Schmidt S, Tegeder M. Transporters for uptake and allocation of organic nitrogen compounds in plants. FEBS Lett. 2007;581:2281-9 pubmed
    ..The review summarizes our current understanding of the molecular mechanisms of organic nitrogen transport processes, with a focus on amino acid, ureide and peptide transporters. ..
  12. Ericsson A, Säljö K, Sjöstrand E, Jansson N, Prasad P, Powell T, et al. Brief hyperglycaemia in the early pregnant rat increases fetal weight at term by stimulating placental growth and affecting placental nutrient transport. J Physiol. 2007;581:1323-32 pubmed
    ..We speculate that maternal metabolism in early pregnancy represents a key environmental cue to which the placenta responds in order to match fetal growth rate with the available resources of the mother...
  13. Nikko E, Andre B. Evidence for a direct role of the Doa4 deubiquitinating enzyme in protein sorting into the MVB pathway. Traffic. 2007;8:566-81 pubmed
    ..We propose that deubiquitination by Doa4 of cargo proteins and/or some components of the MVB sorting machinery is essential to correct sorting of cargoes into the MVB pathway. ..
  14. Thwaites D, Anderson C. The SLC36 family of proton-coupled amino acid transporters and their potential role in drug transport. Br J Pharmacol. 2011;164:1802-16 pubmed publisher
  15. Pinto V, Pinho M, Soares da Silva P. Renal amino acid transport systems and essential hypertension. FASEB J. 2013;27:2927-38 pubmed publisher
    ..The study of the regulation of renal amino acid transporters may help to define the underlying mechanisms predisposing individuals to an increased risk for development of hypertension. ..
  16. Dorn M, Weiwad M, Markwardt F, Laug L, Rudolph R, Brandsch M, et al. Identification of a disulfide bridge essential for transport function of the human proton-coupled amino acid transporter hPAT1. J Biol Chem. 2009;284:22123-32 pubmed publisher
    ..This disulfide bridge is very likely involved in forming or stabilizing the substrate binding site. ..
  17. Lehmann S, Funck D, Szabados L, Rentsch D. Proline metabolism and transport in plant development. Amino Acids. 2010;39:949-62 pubmed publisher
    ..Additional information from animals, fungi and bacteria is included, showing similarities and differences to proline metabolism and transport in plants. ..
  18. Sharma C, Papenfort K, Pernitzsch S, Mollenkopf H, Hinton J, Vogel J. Pervasive post-transcriptional control of genes involved in amino acid metabolism by the Hfq-dependent GcvB small RNA. Mol Microbiol. 2011;81:1144-65 pubmed publisher
    ..Rather, GcvB rewires primary transcriptional control circuits and seems to act as a distinct regulatory node in amino acid metabolism. ..
  19. Kota J, Gilstring C, Ljungdahl P. Membrane chaperone Shr3 assists in folding amino acid permeases preventing precocious ERAD. J Cell Biol. 2007;176:617-28 pubmed
    ..Consequently, in cells with impaired ERAD, AAPs are able to attain functional conformations independent of Shr3. These findings illustrate that folding and degradation are tightly coupled processes during membrane protein biogenesis. ..
  20. Gao X, Lu F, Zhou L, Dang S, Sun L, Li X, et al. Structure and mechanism of an amino acid antiporter. Science. 2009;324:1565-8 pubmed publisher
    ..A conserved, acidic pocket opens to the periplasm. Structural and biochemical analysis reveals the essential ligand-binding residues, defines the transport route, and suggests a conserved mechanism for the antiporter activity. ..
  21. Uemura T, Kashiwagi K, Igarashi K. Polyamine uptake by DUR3 and SAM3 in Saccharomyces cerevisiae. J Biol Chem. 2007;282:7733-41 pubmed
    ..It was found that DUR3 (but not SAM3) was activated by phosphorylation of Thr(250), Ser(251), and Thr(684) by polyamine transport protein kinase 2. ..
  22. Kashiwagi H, Yamazaki K, Takekuma Y, Ganapathy V, Sugawara M. Regulatory mechanisms of SNAT2, an amino acid transporter, in L6 rat skeletal muscle cells by insulin, osmotic shock and amino acid deprivation. Amino Acids. 2009;36:219-30 pubmed publisher
    ..Western blot and RT-PCR analysis showed an increase in system A at the protein and mRNA levels with each stimulation. ..
  23. Risinger A, Kaiser C. Different ubiquitin signals act at the Golgi and plasma membrane to direct GAP1 trafficking. Mol Biol Cell. 2008;19:2962-72 pubmed publisher
  24. Perez C, Ziegler C. Mechanistic aspects of sodium-binding sites in LeuT-like fold symporters. Biol Chem. 2013;394:641-8 pubmed publisher
    ..Moreover, we highlight their crucial roles in conformational changes of LeuT-like fold transporters and their implication on a unifying mechanism in secondary transport. ..
  25. Lauwers E, Grossmann G, Andre B. Evidence for coupled biogenesis of yeast Gap1 permease and sphingolipids: essential role in transport activity and normal control by ubiquitination. Mol Biol Cell. 2007;18:3068-80 pubmed
    ..We propose that coupled biogenesis of Gap1 and SLs would create an SL microenvironment essential to the normal conformation, function, and control of ubiquitination of the permease. ..
  26. Garrett J. Amino acid transport through the Saccharomyces cerevisiae Gap1 permease is controlled by the Ras/cAMP pathway. Int J Biochem Cell Biol. 2008;40:496-502 pubmed
    ..A mechanism by which the Ras2/cAMP/PKA pathway controls the ubiquitin-dependent degradation of Gap1p is most consistent with the data. ..
  27. Reynolds B, Laynes R, Ogmundsdóttir M, Boyd C, Goberdhan D. Amino acid transporters and nutrient-sensing mechanisms: new targets for treating insulin-linked disorders?. Biochem Soc Trans. 2007;35:1215-7 pubmed
  28. Van Zeebroeck G, Kimpe M, Vandormael P, Thevelein J. A split-ubiquitin two-hybrid screen for proteins physically interacting with the yeast amino acid transceptor Gap1 and ammonium transceptor Mep2. PLoS ONE. 2011;6:e24275 pubmed publisher
    ..They provide several candidate proteins involved in the transport and signaling function or in the complex trafficking control of the Gap1 and Mep2 transceptors. ..
  29. Van Zeebroeck G, Bonini B, Versele M, Thevelein J. Transport and signaling via the amino acid binding site of the yeast Gap1 amino acid transceptor. Nat Chem Biol. 2009;5:45-52 pubmed publisher
    ..They indicate that signaling requires a ligand-induced specific conformational change that may be part of but does not require the complete transport cycle. ..
  30. Roumelioti K, Vangelatos I, Sophianopoulou V. A cryptic role of a glycolytic-gluconeogenic enzyme (aldolase) in amino acid transporter turnover in Aspergillus nidulans. Fungal Genet Biol. 2010;47:254-67 pubmed publisher
    ..Our results support a novel role of the FbaA protein that is, involvement in the regulation of amino acids transporters. ..
  31. Ladwig F, Stahl M, Ludewig U, Hirner A, Hammes U, Stadler R, et al. Siliques are Red1 from Arabidopsis acts as a bidirectional amino acid transporter that is crucial for the amino acid homeostasis of siliques. Plant Physiol. 2012;158:1643-55 pubmed publisher
    ..Our data demonstrate that the SIAR1-mediated export of amino acids plays an important role in organic nitrogen allocation and particularly in amino acid homeostasis in developing siliques. ..
  32. Rubio Texeira M, Van Zeebroeck G, Thevelein J. Peptides induce persistent signaling from endosomes by a nutrient transceptor. Nat Chem Biol. 2012;8:400-8 pubmed publisher
    ..Hence, this work has identified specific dipeptides that cause enhanced proton influx through the Gap1 symporter, resulting in its defective vacuolar sorting, and independently transform it into a persistently signaling transceptor. ..
  33. Apostolaki A, Erpapazoglou Z, Harispe L, Billini M, Kafasla P, Kizis D, et al. AgtA, the dicarboxylic amino acid transporter of Aspergillus nidulans, is concertedly down-regulated by exquisite sensitivity to nitrogen metabolite repression and ammonium-elicited endocytosis. Eukaryot Cell. 2009;8:339-52 pubmed publisher
    ..Thus, nitrogen metabolite repression and ammonium-promoted vacuolar degradation act in concert to downregulate dicarboxylic amino acid transport activity. ..
  34. Lauwers E, Jacob C, Andre B. K63-linked ubiquitin chains as a specific signal for protein sorting into the multivesicular body pathway. J Cell Biol. 2009;185:493-502 pubmed publisher
    ..Our data reveal that K63-linked Ub chains act as a specific signal for MVB sorting, providing further insight into the Ub code of membrane protein trafficking. ..
  35. Rubio Texeira M. Urmylation controls Nil1p and Gln3p-dependent expression of nitrogen-catabolite repressed genes in Saccharomyces cerevisiae. FEBS Lett. 2007;581:541-50 pubmed
    ..Altogether, the data presented here indicate an important role of the urmylation pathway in regulating the expression of genes involved in sensing and controlling amino acids levels. ..
  36. Nakase M, Nakase Y, Chardwiriyapreecha S, Kakinuma Y, Matsumoto T, Takegawa K. Intracellular trafficking and ubiquitination of the Schizosaccharomyces pombe amino acid permease Aat1p. Microbiology. 2012;158:659-73 pubmed publisher
    ..These results indicate that ubiquitination is an important determinant for localization and regulation of the Aat1p permease in S. pombe. ..
  37. Matsui T, Fukuda M. Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4. EMBO Rep. 2013;14:450-7 pubmed publisher
    ..Our findings reveal a new mechanism of regulation of mTORC1 signalling and autophagy, that is, quality control of PAT4 by Rab12. ..
  38. Liu B, Du H, Rutkowski R, Gartner A, Wang X. LAAT-1 is the lysosomal lysine/arginine transporter that maintains amino acid homeostasis. Science. 2012;337:351-4 pubmed publisher
    ..Thus, LAAT-1 is the lysosomal lysine/arginine transporter, which suggests a molecular explanation for how cysteamine alleviates a lysosomal storage disease. ..
  39. Marella H, Nielsen E, Schachtman D, Taylor C. The amino acid permeases AAP3 and AAP6 are involved in root-knot nematode parasitism of Arabidopsis. Mol Plant Microbe Interact. 2013;26:44-54 pubmed publisher
    ..The transport of amino acids by AAP3 and AAP6 is important for nematode infection and success of the progeny. ..
  40. Merhi A, Gérard N, Lauwers E, Prevost M, Andre B. Systematic mutational analysis of the intracellular regions of yeast Gap1 permease. PLoS ONE. 2011;6:e18457 pubmed publisher
    ..Interestingly, this direct vacuolar sorting seems to be independent of Gap1 ubiquitylation. This study illustrates the importance of multiple intracellular regions of Gap1 in its secretion, transport activity, and down-regulation. ..
  41. Kanneganti V, Kama R, Gerst J. Btn3 is a negative regulator of Btn2-mediated endosomal protein trafficking and prion curing in yeast. Mol Biol Cell. 2011;22:1648-63 pubmed publisher
    ..Therefore Btn3 is a novel negative regulator of intracellular protein sorting, which may be of importance in the onset of complex I deficiency and Batten disease in humans. ..
  42. Kusinski L, Jones C, Baker P, Sibley C, Glazier J. Isolation of plasma membrane vesicles from mouse placenta at term and measurement of system A and system beta amino acid transporter activity. Placenta. 2010;31:53-9 pubmed publisher
    ..This mirrored the lower expression of TAUT observed in mouse placental vesicles. We conclude that syncytiotrophoblast layer II-derived plasma membrane vesicles can be isolated and used to examine transporter function. ..
  43. Kraidlova L, Van Zeebroeck G, Van Dijck P, Sychrova H. The Candida albicans GAP gene family encodes permeases involved in general and specific amino acid uptake and sensing. Eukaryot Cell. 2011;10:1219-29 pubmed publisher
    ..Our data show that CaGAP genes can be functionally expressed in S. cerevisiae and that CaGap permeases communicate to the intracellular signal transduction pathway similarly to ScGap1. ..
  44. Kriel J, Haesendonckx S, Rubio Texeira M, Van Zeebroeck G, Thevelein J. From transporter to transceptor: signaling from transporters provokes re-evaluation of complex trafficking and regulatory controls: endocytic internalization and intracellular trafficking of nutrient transceptors may, at least in part, be governed by. Bioessays. 2011;33:870-9 pubmed publisher
    ..Hence, precise regulation of intracellular trafficking in nutrient transporters may be related to the need for tight control of nutrient-induced signaling. ..
  45. Cain N, Kaiser C. Transport activity-dependent intracellular sorting of the yeast general amino acid permease. Mol Biol Cell. 2011;22:1919-29 pubmed publisher
    ..These results indicate a parsimonious regulatory mechanism by which Gap1p senses its transport substrates to set an appropriate level of transporter activity at the cell surface. ..
  46. Binda M, Péli Gulli M, Bonfils G, Panchaud N, Urban J, Sturgill T, et al. The Vam6 GEF controls TORC1 by activating the EGO complex. Mol Cell. 2009;35:563-73 pubmed publisher
    ..Thus, in addition to its regulatory role in homotypic vacuolar fusion and vacuole protein sorting within the HOPS complex, Vam6 also controls TORC1 function by activating the Gtr1 subunit of the EGO complex. ..
  47. Ogmundsdóttir M, Heublein S, Kazi S, Reynolds B, Visvalingam S, Shaw M, et al. Proton-assisted amino acid transporter PAT1 complexes with Rag GTPases and activates TORC1 on late endosomal and lysosomal membranes. PLoS ONE. 2012;7:e36616 pubmed publisher
    ..In light of the recent identification of the vacuolar H(+)-ATPase as another Rag-interacting component, we propose a model in which PATs function as part of an AA-sensing engine that drives mTORC1 activation from LEL compartments. ..
  48. Vangelatos I, Vlachakis D, Sophianopoulou V, Diallinas G. Modelling and mutational evidence identify the substrate binding site and functional elements in APC amino acid transporters. Mol Membr Biol. 2009;26:356-70 pubmed publisher
  49. Fang Y, Jayaram H, Shane T, Kolmakova Partensky L, Wu F, Williams C, et al. Structure of a prokaryotic virtual proton pump at 3.2 A resolution. Nature. 2009;460:1040-3 pubmed publisher
    ..2 A resolution. The protein is captured in an outward-open, substrate-free conformation with transmembrane architecture remarkably similar to that seen in four other families of apparently unrelated transport proteins. ..
  50. Hundal H, Taylor P. Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling. Am J Physiol Endocrinol Metab. 2009;296:E603-13 pubmed publisher
    ..We hypothesize (by extrapolation from knowledge of the yeast Ssy1 transceptor) that, at least for SNAT2, the transceptor discriminates between extracellular and intracellular amino acid stimuli when evoking a signal. ..
  51. Singh S, Piscitelli C, Yamashita A, Gouaux E. A competitive inhibitor traps LeuT in an open-to-out conformation. Science. 2008;322:1655-61 pubmed publisher
  52. Casagrande F, Ratera M, Schenk A, Chami M, Valencia E, Lopez J, et al. Projection structure of a member of the amino acid/polyamine/organocation transporter superfamily. J Biol Chem. 2008;283:33240-8 pubmed publisher
    ..Thus, two-dimensional crystals of AdiC-W293L yielded the first detailed view of a transport protein from the APC superfamily at sub-nanometer resolution...
  53. Jackson A. Origins of amino acid transporter loci in trypanosomatid parasites. BMC Evol Biol. 2007;7:26 pubmed
    ..Not least in T. brucei, which seems to have retained fewer ancestral loci and has acquired novel loci through a complex mix of tandem and transpositive duplication. ..