Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Apr 13:15:670346.
doi: 10.3389/fncel.2021.670346. eCollection 2021.

Regulation of Glutamate, GABA and Dopamine Transporter Uptake, Surface Mobility and Expression

Renae M Ryan  1 , Susan L Ingram  2 , Annalisa Scimemi  3
Affiliations
Review

Regulation of Glutamate, GABA and Dopamine Transporter Uptake, Surface Mobility and Expression

Renae M Ryan et al. Front Cell Neurosci. .

Abstract

Neurotransmitter transporters limit spillover between synapses and maintain the extracellular neurotransmitter concentration at low yet physiologically meaningful levels. They also exert a key role in providing precursors for neurotransmitter biosynthesis. In many cases, neurons and astrocytes contain a large intracellular pool of transporters that can be redistributed and stabilized in the plasma membrane following activation of different signaling pathways. This means that the uptake capacity of the brain neuropil for different neurotransmitters can be dynamically regulated over the course of minutes, as an indirect consequence of changes in neuronal activity, blood flow, cell-to-cell interactions, etc. Here we discuss recent advances in the mechanisms that control the cell membrane trafficking and biophysical properties of transporters for the excitatory, inhibitory and modulatory neurotransmitters glutamate, GABA, and dopamine.

Keywords: GABA; dopamine; glutamate; surface mobility; transporter; uptake.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Crystal structure of GltPh, a bacterial homolog of glutamate transporters (PDB: 2NWX). (A) Side view of the glutamate transporter trimer parallel to the membrane, using a ribbon (top) and a surface representation sliced through the center of the transporter basin (bottom). (B) As in A, viewed from the extracellular side of the membrane. Aspartate (magenta) and sodium ions (blue) are represented as spheres. (C) Summary of the main feature of the stoichiometric and non-stoichiometric current mediated by glutamate transporters in prokaryotes and eukaryotes, respectively. Image generated using The PyMOL Molecular Graphics System (Version 2.3.2; Schrödinger, 2010).
FIGURE 2
FIGURE 2
Crystal structure of LeuTAA, a bacterial homolog of GABA transporters (PDB: 2A65). (A) Side view of the LeuTAa transporter parallel to the membrane, using a ribbon (top) and a surface representation sliced through the center of the transporter (bottom). (B) As in (A), viewed from the extracellular side of the membrane. Leu (magenta), sodium (blue), and chloride ions (green) are represented as spheres. (C) Summary of the main feature of the stoichiometric and non-stoichiometric current mediated by Leu and GABA transporters in prokaryotes and eukaryotes, respectively. Image generated using The PyMOL Molecular Graphics System (Version 2.3.2; Schrödinger, 2010).
FIGURE 3
FIGURE 3
Crystal structure of Drosophila melanogaster dDAT dopamine transporter (PDB: 4XP1). (A) Side view of the Drosophila dopamine transporter parallel to the membrane, using a ribbon (top) and a surface representation sliced through the center of the transporter (bottom). (B) As in A, viewed from the extracellular side of the membrane. L-Dopa (magenta), sodium (blue) and chloride ions (green) are represented as spheres. (C) Summary of the main feature of the stoichiometric and non-stoichiometric current mediated by LeuT (prokaryotic dopamine transporter homolog) and DAT transporters in eukaryotes, respectively. Image generated using The PyMOL Molecular Graphics System (Version 2.3.2; Schrödinger, 2010).
See this image and copyright information in PMC

References

    1. Adkins E. M., Samuvel D. J., Fog J. U., Eriksen J., Jayanthi L. D., Vaegter C. B., et al. (2007). Membrane mobility and microdomain association of the dopamine transporter studied with fluorescence correlation spectroscopy and fluorescence recovery after photobleaching. Biochemistry 46 10484–10497. 10.1021/bi700429z - DOI - PubMed
    1. Adolph O., Koster S., Rath M., Georgieff M., Weigt H. U., Engele J., et al. (2007). Rapid increase of glial glutamate uptake via blockade of the protein kinase A pathway. Glia 55 1699–1707. 10.1002/glia.20583 - DOI - PubMed
    1. Aggarwal S., Mortensen O. V. (2017). Overview of monoamine transporters. Curr. Protoc. Pharmacol. 79 12.16.1–12.16.17. 10.1002/cpph.32 - DOI - PMC - PubMed
    1. Al Awabdh S., Gupta-Agarwal S., Sheehan D. F., Muir J., Norkett R., Twelvetrees A. E., et al. (2016). Neuronal activity mediated regulation of glutamate transporter GLT-1 surface diffusion in rat astrocytes in dissociated and slice cultures. Glia 64 1252–1264. 10.1002/glia.22997 - DOI - PMC - PubMed
    1. Anderson B. B., Chen G., Gutman D. A., Ewing A. G. (1998). Dopamine levels of two classes of vesicles are differentially depleted by amphetamine. Brain Res. 788 294–301. 10.1016/s0006-8993(98)00040-7 - DOI - PubMed

LinkOut - more resources