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Insights From Endogenous and Engineered Zn2+ Binding Sites in Monoamine Transporters

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Molecular Neuropharmacology

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Abstract

The availability in the synaptic cleft of dopamine, serotonin, and norepinephrine, referred to as the monoamines, is tightly regulated by specific transport proteins that mediate rapid uptake into the presynaptic nerve terminals utilizing the Na+ gradient across the plasma membrane as the driving force (1–3). Three distinct monoamine transporters have been identified: the dopamine transporter (DAT) (Fig. 1), the norepinephrine transporter (NET), and the serotonin transporter (SERT) (1–3). These transporters belong to the family of Na+/C1−-coupled transporters that also include transporters for other neurotransmitters such as GABA (γ-aminobutyric acid) and glycine (1–3). The homology among the Na+/Cl−-dependent neurotransmitter transporters is striking with, e.g., 67% sequence identity between DAT and NET, 49% between DAT and SERT, and 45% between DAT and the (GABA transporter-1 (GAT-1) (2,4). Recently, it has become clear that homologs of Na+/Cl−-dependent transporters also exist in prokaryotes. BLAST searches of newly sequenced bacterial genomes have revealed the existence of genes in many bacteria and archae (~50) encoding proteins with up to 25% sequence identity with the human DAT (see also Chapter 12). The function of these putative transporters is unknown, except that one transporter from the thermophilic bacteria Symbiobacterium Thermophillum very recently has been identified as a highly selective tryptophan transporter (5).

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  1. Claus Juul Loland
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  2. Ulrik Gether
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  1. Department of Pharmacology, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark

    Arne Schousboe PhD, DSc

  2. Department of Medical Chemistry, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark

    Hans Bräuner-Osborne PhD, DSc

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Loland, C.J., Gether, U. (2004). Insights From Endogenous and Engineered Zn2+ Binding Sites in Monoamine Transporters. In: Schousboe, A., Bräuner-Osborne, H. (eds) Molecular Neuropharmacology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-672-0_11

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