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Monoamine Transporters in the Brain

Structure and Function

  • Reference work entry
  • First Online:
Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

Monoamine transporters mediate the uptake of serotonin (SERT), norepinephrine (NET), and dopamine (DAT). They are closely related, share many conserved sequence elements and thus overlapping specificities for binding of inhibitors and substrates. The transporter is thought to undergo a conformational cycle that allows for transmembrane translocation of the monoamine substrate and the cosubstrate ions Na+ and Cl−. In addition, transporters are known to support currents that are substantially larger than those anticipated from the movement of charges during a translocation cycle. The recently solved structure of the distantly related bacterial leucine transporter (LeuTAa) offers insights that allow to reconcile the channel-like mode in which transporters can operate with the original alternate access model. Access to the substrate and cosubstrate permeation pathway is shielded by juxtamembrane residues, which can operate as gates. When simultaneously open, they allow for large ion fluxes which give rise to excess currents. SERT, NET, and DAT and the other (related) members of the Na+-dependent neurotransmitter family form constitutive oligomers. Oligomerization is a prerequisite for export of the proteins from the endoplasmic reticulum (ER) because it supports the recruitment of COPII components, most notably Sec24-family members. In addition, the action of amphetamines which induce reverse transport and thus monoamine efflux is proposed to be contingent on the oligomeric assembly of transporters.

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Abbreviations

COPII:

coat protein II

DAT:

dopamine transporter

ER:

endoplasmic reticulum

ERES:

ER exit sites

FRET:

Fluorescence resonance energy transfer

GABA:

γ‐amino butyric acid

GAT1:

GABA transporter 1

GEF:

guanine nucleotide exchange factor

5‐HT:

serotonin

LeuTAa :

leucine transporter

MDMA:

methylene‐dioxymethamphetamine

MTS:

methanethiosulfonate

MTSEA:

MTS ethylammonium

MTSET:

MTS‐ethyltrimethylammonium

MTSES:

MTS‐ethylsulfonate

NET:

norepinephrine transporter

PCA:

para‐chloroamphetamine

SERT:

serotonin transporter

SNAP25:

synaptosomal‐associated protein of 25 kDa

TM:

transmembrane domain

VAMP:

vesicle associated membrane protein

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Acknowledgments

The authors wish to acknowledge support by the following granting institutions: grant P17076 and P18076 (to HHS) from the Austrian Science Foundation/FWF.

Authors
  1. H. H. Sitte
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  2. M. Freissmuth
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, New York, 10962, Orangeburg, USA

    Abel Lajtha

  2. Department of Psychiatry Millhauser Labs, Room MHL‐HN–604A, New York University School of Medicine, 550 First Avenue, N.Y. 10016, New York, USA

    Maarten E. A. Reith Ph.D.

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Sitte, H.H., Freissmuth, M. (2007). Monoamine Transporters in the Brain. In: Lajtha, A., Reith, M.E.A. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30380-2_17

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