Skip to main content
SpringerLink
Log in

Structure and Function of GABA Reuptake Systems

  • Chapter
The GABA Receptors

Part of the book series: The Receptors ((REC))

Abstract

High affinity sodium-coupled transport systems are responsible for the reuptake of neurotransmitters from the synaptic cleft. They appear to play an important role in the overall process of synaptic transmission, namely in its termination (Iversen, 1971, 1973). The process is catalyzed by sodium-coupled neurotransmitter transport systems located in plasma membranes of nerve endings and glial cells (Kanner, 1983, 1989; Kanner and Schuldiner, 1987). These transport systems have been investigated in detail by using plasma membranes obtained upon osmotic shock of synaptosomes. It appears that these transporters are coupled not only to sodium, but also to additional ions like potassium or chloride.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Bendahan, A. and Kanner, B. I. (1993) Identification of domains of a cloned rat brain GABA transporter which are not required for its functional expression. FEBS Lett. 318, 41–44.

    Article  PubMed  CAS  Google Scholar 

  • Blakely, R. D., Benson, H. E., Fremeau, R. T., Jr., Caron, M. G., Peek, M. M., Prince, H. K., and Bradley, C. C. (1991) Cloning and expression of a functional serotonin transporter from rat brain. Nature 353, 66–70.

    Article  Google Scholar 

  • Borden, L. A., Smith, K. E., Hartig, R. R., Branchek, T. A., and Weinshank, R. L. (1992) Molecular heterogeneity of the GABA transport system. J. Biol. Chem. 267, 21098–21104.

    PubMed  CAS  Google Scholar 

  • Clark, J. A., Deutch, A. Y., Gallipoli, R. Z., and Amara, S. G. (1992) Functional expression and CNS distribution of (3-alanine sensitive neuronal GABA transporter. Neuron 9, 337–348.

    Article  PubMed  CAS  Google Scholar 

  • Fremeau, R. T., Jr., Caron, M. G., and Blakely, R. D. (1992) Molecular cloning and expression of a high affinity 1-proline transporter expressed in putative glutamatergic pathways of rat brain. Neuron 8, 915–926.

    Article  PubMed  CAS  Google Scholar 

  • Guastella, J., Brecha, N., Weigmann, C., and Lester, H. A. (1992) Cloning, expression and localization of a rat brain high affinity glycine transporter. Proc. Natl. Acad. Sci. USA 89, 7189–7193.

    Article  PubMed  CAS  Google Scholar 

  • Guastella, J., Nelson, N., Nelson, H., Czyzyk, L., Keynan, S., Miedel, M. C., Davidson, N. C., Lester, H. A., and Kanner, B. I. (1990) Cloning and expression of a rat brain GABA transporter. Science 249, 1303–1306.

    Article  PubMed  CAS  Google Scholar 

  • Guimbal, C. and Kilimann, M. W. (1993) A Na. dependent creatine transporter in rabbit brain, muscle, heart and kidney. cDNA cloning and functional expression. J. Biol. Chem. 268, 8418–8421.

    PubMed  CAS  Google Scholar 

  • Hoffman, B. J., Mezey, E., and Brownstein, M. J. (1991) Cloning of a serotonin transporter affected by antidepressants. Science 254, 579–580.

    Google Scholar 

  • Iversen, L. L. (1971) Role of transmitter uptake mechanism in synaptic neurotransmission. Br. J. Pharmacol. 41, 571–591.

    Google Scholar 

  • Kanner, B. I. (1983) Bioenergetics of neurotransmitter transport. Biochim. Biophys. Acta 726, 293–316.

    Article  PubMed  CAS  Google Scholar 

  • Kanner, B. I. (1989) Ion-coupled neurotransmitter transporter. Curr. Opin. Cell Biol. 1, 735–738.

    Article  PubMed  CAS  Google Scholar 

  • Kanner, B. I. (1993) Glutamate transporters from brain: a novel neurotransmitter transporter family. FEBS Lett. 325, 95–99.

    Article  PubMed  CAS  Google Scholar 

  • Kanner, B. I. and Bendahan, A. (1990) Two pharmacologically distinct sodium-and chloride-coupled high-affinity y-aminobutyric acid transporters are present in plasma membrane vesicles and reconstituted preparations from rat brain. Proc. Natl. Acad. Sci. USA 87, 2550–2554.

    Article  PubMed  CAS  Google Scholar 

  • Kanner, B. I., Bendahan, A., Pantanowitz, S., and Su, H. (1994) The number of amino acid residues in hydrophilic loops connecting transmembrane domains of the GABA transporter GAT-1 is critical for its function. FEBS Lett. 356, 191–194.

    Article  PubMed  CAS  Google Scholar 

  • Kanner, B. I., Keynan, S., and Radian, R. (1989) Structural and functional studies on the sodium and chloride-coupled y-aminobutyric acid transporter. Deglycosylation and limited proteolysis. Biochemistry 28, 3722–3727.

    Article  PubMed  CAS  Google Scholar 

  • Kanner, B. I. and Schuldiner, S. (1987) Mechanism of transport and storage of neurotransmitters. CRC Crit. Rev. Biochem. 22, 1–39.

    Article  PubMed  CAS  Google Scholar 

  • Kavanaugh, M. P., Arriza, J. L., North, R. A., and Amara, S. G. (1992) Electrogenic uptake of y-aminobutyric acid by a cloned transporter expressed in oocytes. J. Biol. Chem. 267, 22007–22009.

    PubMed  CAS  Google Scholar 

  • Keynan, S. and Kanner, B. I. (1988) y-Aminobutyric acid transport in reconstituted preparations from rat brain: coupled sodium and chloride fluxes. Biochemistry 27, 12–17.

    Google Scholar 

  • Kilty, J. E., Lorang, D., and Amara, S. G. (1991) Cloning and expression of a cocainesensitive rat dopamine transporter. Science 254, 578–579.

    Article  PubMed  CAS  Google Scholar 

  • Kitayama, S., Shimada, S., Xu, H., Markham, L., Donovan, D. M., and Uhl, G. R. (1992) Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine binding. Proc. Natl. Acad. Sci. USA 89, 7782–7785.

    Article  PubMed  CAS  Google Scholar 

  • Kleinberger-Doron, N., and Kanner, B. I. (1994) Identification of tryptophan residues critical for the function and targeting of the y-aminobutyric acid transporter (subtype A). J. Biol. Chem. 269, 3063–3067.

    PubMed  CAS  Google Scholar 

  • Kuhar, M. J. (1973) Neurotransmitter uptake: a tool in identifying neurotransmitter-specific pathways. Life Sci. 13, 1623–1634.

    Article  PubMed  CAS  Google Scholar 

  • Kuhar, M. J. and Zarbin, M. A. (1978) Synaptosomal transport: a chloride dependence for choline, GABA, glycine and several other compounds. J. Neurochem. 31, 251–256.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Q. R., Lopez-Corcuera, B., Nelson, H., Mandiyan, S., and Nelson, N. (1992a) Cloning and expression of a cDNA encoding the transporter of taurine and 0-alanine in mouse brain. Proc. Natl. Acad. Sci. USA 89, 12,145–12, 149.

    Google Scholar 

  • Liu, Q. R., Nelson, H., Mandiyan, S., Lopez-Corcuera, B., and Nelson, N. (1992b) Cloning and expression of a glycine transporter from mouse brain. FEBS Lett. 305, 110–114.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Q. R., Lopez-Corcuera, B., Mandiyan, S., Nelson, H., and Nelson, N. (1993a) Molecular characterization of four pharmacologically distinct y-aminobutyric acid transporters in mouse brain. J. Biol. Chem. 268, 2104–2112.

    Google Scholar 

  • Liu, Q. R., Mandiyan, S., Lopez-Corcuera, B., Nelson, H., and Nelson, N. (1993b) A rat brain cDNA encoding the neurotransmitter transporter with an unusual structure. FEBS Lett. 315, 114–118.

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Corcuera, B., Liu, Q. R., Mandiyan, S., Nelson, H., and Nelson, N. (1992) Expression of a mouse brain cDNA encoding novel y-aminobutyric acid transporter. J. Biol. Chem. 267, 17491–17493.

    PubMed  CAS  Google Scholar 

  • Lopez-Corcuera, B., Vazquez, J., and Aragon, C. (1991) Purification of the sodium-and chloride-coupled glycine transporter from central nervous system. J. Biol. Chem. 266, 24809–24814.

    PubMed  CAS  Google Scholar 

  • Mabjeesh, N. J. and Kanner, B. I. (1989) Low affinity y-aminobutyric acid transport in rat brain. Biochemistry 28, 7694–7699.

    Article  PubMed  CAS  Google Scholar 

  • Mabjeesh, N. J. and Kanner, B. I. (1992) Neither amino nor carboxyl termini are required for function of the sodium-and chloride-coupled y-aminobutyric acid transporter from rat brain. J. Biol. Chem. 267, 2563–2568.

    PubMed  CAS  Google Scholar 

  • Mabjeesh, N. J. and Kanner, B. I. (1993) The substrates of a sodium-and chloride-coupled y-aminobutyric acid transporter protect multiple sites throughout the protein against proteolytic cleavage. Biochemistry 32, 8540–8546.

    Article  PubMed  CAS  Google Scholar 

  • Mager, S., Naeve, J., Quick, M., Labarca, C., Davidson, N., and. Lester, H. A. (1993) Steady states, charge movements and rates for a cloned GABA transporter expressed in Xenopus oocytes. Neuron 10, 177–188.

    CAS  Google Scholar 

  • Mayser, W., Schloss, P., and Betz, H. (1992) Primary structure and functional expression of a choline transporter expressed in the rat nervous system. FEBS Lett. 305, 31–36.

    Article  PubMed  CAS  Google Scholar 

  • Pacholczyk, T., Blakely, R. D., and Amara, S. G. ( 1991 ) Expression cloning of a cocaine and antidepressant-sensitive human noradrenaline transporter. Nature 350, 350–354.

    Article  PubMed  CAS  Google Scholar 

  • Pantanowitz, S., Bendahan, A., and Kanner, E. I. (1993) Only one of the charged amino acids located in the transmembrane a helices of the y-aminobutyric acid transporter (subtype A) is essential for its activity. J. Biol. Chem. 268, 3222–3225.

    PubMed  CAS  Google Scholar 

  • Radian, R., Bendahan, A., and Kanner, B. I. (1986) Purification and identification of the functional sodium-and chloride-coupled y-aminobutyric acid transport glycoprotein from rat brain. J. Biol. Chem. 261, 15437–15441.

    PubMed  CAS  Google Scholar 

  • Radian, R. and Kanner, B. I. (1983) Stoichiometry of sodium-and chloride-coupled yaminobutyric acid transport by synaptic plasma membrane vesicles isolated from rat brain. Biochemistry 22, 1236–1241.

    Article  PubMed  CAS  Google Scholar 

  • Radian, R. and Kanner, B. I. (1985) Reconstitution and purification of the sodium-and chloride-coupled y-aminobutyric acid transporter from rat brain. J. Biol. Chem. 260, 11859–11865.

    PubMed  CAS  Google Scholar 

  • Shimada, S., Kitayama, S., Lin, C. L., Patel, A., Nanthakumar, E., Gregor, P., Kuhar, M., Uhl, G. (1991) Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA. Science 254, 576–578.

    Article  PubMed  CAS  Google Scholar 

  • Smith, K. E., Borden, L. A., Hartig, P. A., Branchek, T., and Weinshank, R. L. (1992) Cloning and expression of a glycine transporter reveal colocalization with NMDA receptors. Neuron 8, 927–935.

    Article  PubMed  CAS  Google Scholar 

  • Sussman, J. L. and Silman, I. (1992) Acetylcholinesterase: structure and use as a model for specific cation-protein interactions. Curt: Opin. Struc. Biol. 2, 721–729.

    Article  CAS  Google Scholar 

  • Uchida, S., Kwon, H. M., Yamauchi, A., Preston, A. S., Marumo, F., and Handler, J. S. (1992) Molecular cloning of the cDNA for an MDCK cell Na+- and Cl--dependent taurine transporter that is regulated by hypertonicity. Proc. Natl. Acad. Sci. USA 89, 8230–8234.

    Article  PubMed  CAS  Google Scholar 

  • Uhl, G. R., Kitayama, S., Gregor, P., Nanthakumer, E., Persico, A., and Shimada, S. (1992) Neurotransmitter transporter family cDNAs in a rat midbrain library: ‘orphan transporters’ suggest sizable structural variations. Mol. Brain Res. 16, 353–359.

    Article  PubMed  CAS  Google Scholar 

  • Usdin, T. B., Mezey, E., Chen, C., Brownstein, M. J., and Hoffman, B. J. (1991) Cloning of the cocaine sensitive bovine dopamine transporter. Proc. Natl. Acad. Sci. USA 88, 11168–11171.

    Article  PubMed  CAS  Google Scholar 

  • Yamauchi, A., Uchida, S., Kwon, H. M., Preston, A. S., Robey, R. B., Garcia-Perez, A., Burg, M. B., and Handler, J. S. (1992) Cloning of a Na+ and Cl-dependent betaine transporter that is regulated by hypertonicity. J. Biol. Chem. 267, 649–652.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Baruch I. Kanner
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical School, Kansas City, KS, USA

    S. J. Enna

  2. Department of Pharmacology, The Medical School Edgbaston, University of Birmingham, UK

    Norman G. Bowery

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kanner, B.I. (1997). Structure and Function of GABA Reuptake Systems. In: Enna, S.J., Bowery, N.G. (eds) The GABA Receptors. The Receptors. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2597-1_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-2597-1_1

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-2599-5

  • Online ISBN: 978-1-4757-2597-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation