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Identification and Characterization of a Novel Monoamine Transporter in the Human Brain

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Engel, Karen, Zhou, Mingyan, Wang, Joanne·2004·Journal of Biological Chemistry

Abstract

Precise control of monoamine neurotransmitter levels in the extracellular fluids of the brain is critical in maintaining efficient and robust neurotransmission. High affinity transporters in the solute carrier SLC6A family function in removing monoamines from the neurosynaptic cleft. Emerging evidence suggests that these transporters are only one part of a system of transporters that work in concert to maintain brain homeostasis of monoamines. Here we report the cloning and characterization of a new human plasma membrane monoamine transporter, PMAT. The PMAT cDNA encodes a protein of 530 amino acid residues with 10-12 transmembrane segments. PMAT is not homologous to known neurotransmitter transporters but exhibits low homology to members of the equilibrative nucleoside transporter family. When expressed in Madin-Darby canine kidney cells and Xenopus laevis oocytes, PMAT efficiently transports serotonin (K(m) = 114 mum), dopamine (K(m) = 329 mum), and the neurotoxin 1-methyl-4-phenylpyridinium (K(m) = 33 mum). In contrast, there is no significant interaction of PMAT with nucleosides or nucleobases. PMAT-mediated monoamine transport does not require Na(+) or Cl(-) but appears to be sensitive to changes in membrane potential. Northern blot analysis showed that PMAT is predominantly expressed in the human brain and widely distributed in the central nervous system. These studies demonstrate that PMAT may be a novel low affinity transporter for biogenic amines, which, under certain conditions, might supplement the role of the high affinity transporters in the brain.

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Metadata

Authors
Engel, K., Zhou, M., & Wang, J.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2004-11
Volume
279
Issue
48
Pages
50042-50049
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1966752296
Cited by
267
References
26
FWCI
4.23
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Identification and Characterization of a Novel Monoamine Transporter in the Human Brain. https://app.cochat.ai/papers/10.1074/jbc.m407913200
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Engel, K., Zhou, M., & Wang, J. (2004). Identification and Characterization of a Novel Monoamine Transporter in the Human Brain. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m407913200

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