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Medientyp:
E-Artikel
Titel:
Differential regulation of serotonin transporter cell surface expression
Beteiligte:
Lau, Thorsten;
Schloss, Patrick
Erschienen:
Wiley, 2012
Erschienen in:Wiley Interdisciplinary Reviews: Membrane Transport and Signaling
Sprache:
Englisch
DOI:
10.1002/wmts.10
ISSN:
2190-4618;
2190-460X
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>In the central nervous system the efficiency of serotonergic signaling is regulated by the release of serotonin (5‐hydroxytryptamine, 5‐HT), the activity of the neurotransmitter synthesizing enzyme, tryptophane hydroxylase 2, the negative‐modulatory autoreceptors 5HT1A<jats:sub>R</jats:sub>and 5HT1B<jats:sub>R</jats:sub>, and a selective re‐uptake system which transports released serotonin back into serotonergic neurons, the serotonin transporter (SERT). Because SERT directly controls the concentration of extracellular free 5‐HT, drugs as well as intracellular signaling pathways which regulate SERT activity play an important role in modulating serotonergic neurotransmission. SERT activity can be regulated by two different means: (1) regulation of SERT acute activity, that is, substrate affinity and/or maximal transport rate, or (2) by modulation the concentration of SERT molecules on the cell surface of neurons. This can be achieved by translocating SERT molecules from intracellular stores to the cell membrane or by inducing an internalization of SERT from the cell surface SERT to the cell interior (‘transporter trafficking’). In recent years evidence has accumulated that some antidepressants but also drugs of abuse such as cocaine or amphetamines not only block SERT mediated re‐uptake, but also impact on SERT cellular trafficking. In addition, several pathways have been identified, which modulate SERT cell surface expression by influencing the cellular distribution of SERT. This involves kinase/phosphatase‐activated pathways as well as intracellular proteins which upon direct interaction with the transporter promote its internalization from or export to the cell surface.<jats:italic>WIREs Membr Transp Signal</jats:italic>2012,1:259–268. doi: 10.1002/wmts.10</jats:p><jats:p>For further resources related to this article, please visit the<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://wires.wiley.com/remdoi.cgi?doi=10.1002/wmts.10">WIREs website</jats:ext-link>.</jats:p>