Voltage-dependent processes in the electroneutral amino acid exchanger ASCT2

Journal of General Physiology

Volumn 141, Issue 6, 2013, Pages 659-672

  Zander, Catherine B ^a   Albers, Thomas ^a   Grewer, Christof ^a  

^a BINGHAMTON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; AMINO ACID TRANSPORTER; ASCT2 PROTEIN, RAT; CYSTEINE; SERINE; SODIUM;

AMINO ACID SEQUENCE; ANIMAL; ARTICLE; BINDING SITE; CELL STRAIN HEK293; CHEMISTRY; HUMAN; MEMBRANE POTENTIAL; METABOLISM; MOLECULAR DYNAMICS; MOLECULAR GENETICS; PROTEIN TERTIARY STRUCTURE; RAT;

ALANINE; AMINO ACID SEQUENCE; AMINO ACID TRANSPORT SYSTEM ASC; ANIMALS; BINDING SITES; CYSTEINE; HEK293 CELLS; HUMANS; MEMBRANE POTENTIALS; MOLECULAR DYNAMICS SIMULATION; MOLECULAR SEQUENCE DATA; PROTEIN STRUCTURE, TERTIARY; RATS; SERINE; SODIUM;

EID: 84878576023     PISSN: 00221295     EISSN: 15407748     Source Type: Journal    
DOI: 10.1085/jgp.201210948     Document Type: Article

References (50)

1. Albers, T., W. Marsiglia, T. Thomas, A. Gameiro, and C. Grewer. 2012. Defining substrate and blocker activity of alanine-serine-cysteine transporter 2 (ASCT2) ligands with novel serine analogs. Mol. Pharmacol. 81:356-365. http://dx.doi.org/10.1124/mol.111.075648
2. Baker, N.A., D. Sept, S. Joseph, M.J. Holst, and J.A. McCammon. 2001. Electrostatics of nanosystems: application to microtubules and the ribosome. Proc. Natl. Acad. Sci. USA. 98:10037-10041. http://dx.doi .org/10.1073/pnas.181342398
3. Bastug, T., G. Heinzelmann, S. Kuyucak, M. Salim, R.J. Vandenberg, and R.M. Ryan. 2012. Position of the third Na+ site in the aspartate transporter GltPh and the human glutamate transporter, EAAT1. PLoS ONE. 7:e33058. http://dx.doi.org/10.1371/journal.pone.0033058
4. Bergles, D.E., A.V. Tzingounis, and C.E. Jahr. 2002. Comparison of coupled and uncoupled currents during glutamate uptake by GLT-1 transporters. J. Neurosci. 22:10153-10162.
5. Bode, B.P. 2001. Recent molecular advances in mammalian glutamine transport. J. Nutr. 131:2475S-2485S.
6. Boudker, O., R.M. Ryan, D. Yernool, K. Shimamoto, and E. Gouaux. 2007. Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter. Nature. 445:387-393. http://dx.doi.org/10.1038/nature05455
7. Bröer, A., N. Brookes, V. Ganapathy, K.S. Dimmer, C.A. Wagner, F. Lang, and S. Bröer. 1999. The astroglial ASCT2 amino acid transporter as a mediator of glutamine efflux. J. Neurochem. 73:2184-2194.
8. Bröer, A., C. Wagner, F. Lang, and S. Bröer. 2000. Neutral amino acid transporter ASCT2 displays substrate-induced Na+ exchange and a substrate-gated anion conductance. Biochem. J. 346:705-710. http://dx.doi.org/10.1042/0264-6021:3460705
9. Bröer, S., and N. Brookes. 2001. Transfer of glutamine between astrocytes and neurons. J. Neurochem. 77:705-719. http://dx.doi.org/10.1046/j.1471-4159.2001.00322.x
10. Bussolati, O., P.C. Laris, B.M. Rotoli, V. Dall'Asta, and G.C. Gazzola. 1992. Transport system ASC for neutral amino acids. An electroneutral sodium/amino acid cotransport sensitive to the membrane potential. J. Biol. Chem. 267:8330-8335.
11. Callenberg, K.M., O.P. Choudhary, G.L. de Forest, D.W. Gohara, N.A. Baker, and M. Grabe. 2010. APBSmem: a graphical interface for electrostatic calculations at the membrane. PLoS ONE. 5:e12722. http://dx.doi.org/10.1371/journal.pone.0012722
12. Choudhary, O.P., R. Ujwal, W. Kowallis, R. Coalson, J. Abramson, and M. Grabe. 2010. The electrostatics of VDAC: implications for selectivity and gating. J. Mol. Biol. 396:580-592. http://dx.doi.org/ 10.1016/j.jmb.2009.12.006
13. Crisman, T.J., S. Qu, B.I. Kanner, and L.R. Forrest. 2009. Inwardfacing conformation of glutamate transporters as revealed by theirinverted-topology structural repeats. Proc. Natl. Acad. Sci. USA. 106:20752-20757. http://dx.doi.org/10.1073/pnas.0908570106
14. Darden, T., D.M. York, and L. Pedersen. 1993. Particle mesh Ewald: an N log(N) method for Ewald sums in large systems. J. Chem. Phys. 98:10089-10092. http://dx.doi.org/10.1063/1.464397
15. De Weer, P., D.C. Gadsby, and R.F. Rakowski. 1988. Overview: stoichiometry and voltage dependence of the Na/K pump. Prog. Clin. Biol. Res. 268A:421-434.
16. Deitmer, J.W., A. Bröer, and S. Bröer. 2003. Glutamine efflux from astrocytes is mediated by multiple pathways. J. Neurochem. 87:127- 135. http://dx.doi.org/10.1046/j.1471-4159.2003.01981.x
17. Eswar, N., B. John, N. Mirkovic, A. Fiser, V.A. Ilyin, U. Pieper, A.C. Stuart, M.A. Marti-Renom, M.S. Madhusudhan, B. Yerkovich, and A. Sali. 2003. Tools for comparative protein structure modeling and analysis. Nucleic Acids Res. 31:3375-3380. http://dx.doi.org/10.1093/nar/gkg543
18. Forster, I.C., K. Köhler, J. Biber, and H. Murer. 2002. Forging the link between structure and function of electrogenic cotransporters: the renal type IIa Na+/Pi cotransporter as a case study. Prog. Biophys. Mol. Biol. 80:69-108. http://dx.doi.org/10.1016/S0079- 6107(02)00015-9
19. Fuchs, B.C., and B.P. Bode. 2005. Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? Semin. Cancer Biol. 15:254- 266. http://dx.doi.org/10.1016/j.semcancer.2005.04.005
20. Grabe, M., H. Lecar, Y.N. Jan, and L.Y. Jan. 2004. A quantitative assessment of models for voltage-dependent gating of ion channels. Proc. Natl. Acad. Sci. USA. 101:17640-17645. http://dx.doi.org/10.1073/pnas.0408116101
21. Grewer, C., and E. Grabsch. 2004. New inhibitors for the neutral amino acid transporter ASCT2 reveal its Na+-dependent anion leak. J. Physiol. 557:747-759. http://dx.doi.org/10.1113/jphysiol.2004.062521
22. Grewer, C., N. Watzke, T. Rauen, and A. Bicho. 2003. Is the glutamate residue Glu-373 the proton acceptor of the excitatory amino acid carrier 1? J. Biol. Chem. 278:2585-2592. http://dx.doi.org/10.1074/jbc.M207956200
23. Grewer, C., Z. Zhang, J. Mwaura, T. Albers, A. Schwartz, and A. Gameiro. 2012. Charge compensation mechanism of a Na+- coupled, secondary active glutamate transporter. J. Biol. Chem. 287: 26921-26931. http://dx.doi.org/10.1074/jbc.M112.364059
24. Groeneveld, M., and D.J. Slotboom. 2010. Na(+):aspartate coupling stoichiometry in the glutamate transporter homologue Glt(Ph). Biochemistry. 49:3511-3513. http://dx.doi.org/10.1021/bi100430s
25. Heinzelmann, G., T. Bastuǧ, and S. Kuyucak. 2011. Free energy simulations of ligand binding to the aspartate transporter Glt(Ph). Biophys. J. 101:2380-2388. http://dx.doi.org/10.1016/j.bpj.2011.10.010
26. Huang, Z., and E. Tajkhorshid. 2008. Dynamics of the extracellular gate and ion-substrate coupling in the glutamate transporter. Biophys. J. 95:2292-2300. http://dx.doi.org/10.1529/biophysj.108.133421
27. Huang, Z., and E. Tajkhorshid. 2010. Identification of the third Na+ site and the sequence of extracellular binding events in the glutamate transporter. Biophys. J. 99:1416-1425. http://dx.doi.org/10.1016/j.bpj.2010.06.052
28. Humphrey, W., A. Dalke, and K. Schulten. 1996. VMD: visual molecular dynamics. J. Mol. Graph. 14:33-38. http://dx.doi.org/10.1016/0263-7855(96)00018-5
29. Larsson, H.P., X. Wang, B. Lev, I. Baconguis, D.A. Caplan, N.P. Vyleta, H.P. Koch, A. Diez-Sampedro, and S.Y. Noskov. 2010. Evidence for a third sodium-binding site in glutamate transporters suggests an ion/substrate coupling model. Proc. Natl. Acad. Sci. USA. 107:13912-13917. http://dx.doi.org/10.1073/pnas.1006289107
30. Loo, D.D., A. Hazama, S. Supplisson, E. Turk, and E.M. Wright. 1993. Relaxation kinetics of the Na+/glucose cotransporter. Proc. Natl. Acad. Sci. USA. 90:5767-5771. http://dx.doi.org/10.1073/pnas.90.12.5767
31. Lu, C.C., and D.W. Hilgemann. 1999. GAT1 (GABA:Na+:Cl?) cotransport function. Steady state studies in giant Xenopus oocyte membrane patches. J. Gen. Physiol. 114:429-444. http://dx.doi.org/10.1085/jgp.114.3.429
32. Mim, C., Z. Tao, and C. Grewer. 2007. Two conformational changes are associated with glutamate translocation by the glutamate transporter EAAC1. Biochemistry. 46:9007-9018. http://dx.doi.org/10.1021/bi7005465
33. Mwaura, J., Z. Tao, H. James, T. Albers, A. Schwartz, and C. Grewer. 2012. Protonation state of a conserved acidic amino acid involved in Na(+) binding to the glutamate transporter EAAC1. ACS Chem Neurosci. 3:1073-1083. http://dx.doi.org/10.1021/cn300163p
34. Nicklin, P., P. Bergman, B. Zhang, E. Triantafellow, H. Wang, B. Nyfeler, H. Yang, M. Hild, C. Kung, C. Wilson, et al. 2009. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 136:521-534. http://dx.doi.org/10.1016/j.cell.2008.11.044
35. Phillips, J.C., R. Braun, W. Wang, J. Gumbart, E. Tajkhorshid, E. Villa, C. Chipot, R.D. Skeel, L. Kalé, and K. Schulten. 2005. Scalable molecular dynamics with NAMD. J. Comput. Chem. 26: 1781-1802. http://dx.doi.org/10.1002/jcc.20289
36. Pines, G., Y. Zhang, and B.I. Kanner. 1995. Glutamate 404 is involved in the substrate discrimination of GLT-1, a (Na+ + K+)- coupled glutamate transporter from rat brain. J. Biol. Chem. 270:17093-17097. http://dx.doi.org/10.1074/jbc.270.29.17093
37. Reyes, N., C. Ginter, and O. Boudker. 2009. Transport mechanism of a bacterial homologue of glutamate transporters. Nature. 462:880-885. http://dx.doi.org/10.1038/nature08616
38. Rostkowski, M., M.H. Olsson, C.R. Søndergaard, and J.H. Jensen. 2011. Graphical analysis of pH-dependent properties of proteins predicted using PROPKA. BMC Struct. Biol. 11:6. http://dx.doi.org/10.1186/1472-6807-11-6
39. Silva, J.R., H. Pan, D. Wu, A. Nekouzadeh, K.F. Decker, J. Cui, N.A. Baker, D. Sept, and Y. Rudy. 2009. A multiscale model linking ionchannel molecular dynamics and electrostatics to the cardiac action potential. Proc. Natl. Acad. Sci. USA. 106:11102-11106. http://dx.doi.org/10.1073/pnas.0904505106
40. Tao, Z., Z. Zhang, and C. Grewer. 2006. 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. 281:10263-10272. http://dx.doi.org/10.1074/jbc.M510739200
41. Tao, Z., N. Rosental, B.I. Kanner, A. Gameiro, J. Mwaura, and C. Grewer. 2010. Mechanism of cation binding to the glutamate transporter EAAC1 probed with mutation of the conserved amino acid residue Thr101. J. Biol. Chem. 285:17725-17733. http://dx.doi.org/10.1074/jbc.M110.121798
42. Utsunomiya-Tate, N., H. Endou, and Y. Kanai. 1996. Cloning and functional characterization of a system ASC-like Na+-dependent neutral amino acid transporter. J. Biol. Chem. 271:14883-14890. http://dx.doi.org/10.1074/jbc.271.25.14883
43. Valdeolmillos, M., J. García-Sancho, and B. Herreros. 1986. Differential effects of transmembrane potential on two Na+-dependent transport systems for neutral amino acids. Biochim. Biophys. Acta. 858:181-187. http://dx.doi.org/10.1016/0005-2736(86)90304-4
44. Wadiche, J.I., and M.P. Kavanaugh. 1998. Macroscopic and microscopic properties of a cloned glutamate transporter/chloride channel. J. Neurosci. 18:7650-7661.
45. Wadiche, J.I., J.L. Arriza, S.G. Amara, and M.P. Kavanaugh. 1995. Kinetics of a human glutamate transporter. Neuron. 14:1019- 1027. http://dx.doi.org/10.1016/0896-6273(95)90340-2
46. Watzke, N., E. Bamberg, and C. Grewer. 2001. Early intermediates in the transport cycle of the neuronal excitatory amino acid carrier EAAC1. J. Gen. Physiol. 117:547-562. http://dx.doi.org/10.1085/jgp.117.6.547
47. Yernool, D., O. Boudker, Y. Jin, and E. Gouaux. 2004. Structure of a glutamate transporter homologue from Pyrococcus horikoshii. Nature. 431:811-818. http://dx.doi.org/10.1038/nature03018
48. Zerangue, N., and M.P. Kavanaugh. 1996a. ASCT-1 is a neutral amino acid exchanger with chloride channel activity. J. Biol. Chem. 271:27991-27994. http://dx.doi.org/10.1074/jbc.271.45.27991
49. Zerangue, N., and M.P. Kavanaugh. 1996b. Flux coupling in a neuronal glutamate transporter. Nature. 383:634-637. http://dx.doi.org/10.1038/383634a0
50. Zhang, Z., G. Papageorgiou, J.E. Corrie, and C. Grewer. 2007. Pre-steady-state currents in neutral amino acid transporters induced by photolysis of a new caged alanine derivative. Biochemistry. 46:3872-3880. http://dx.doi.org/10.1021/bi0620860