The serotonin transporter (SERT) plays a critical role in the maintenance of normal neurotransmission by serotonin [5-hydroxytryptamine (5-HT)]. Recent evidence suggests that SERT and other neurotransmitter transporters are tightly regulated. Activation of protein kinase C results in a decrease in SERT-mediated 5-HT uptake, which is due to an internalization of the transporter. However, to date little is known about the mechanism and proteins involved in the down-regulation of the transporter. One candidate SERT-regulatory protein is the SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) protein, syntaxin 1A (Syn1A), which has recently been implicated in the regulation of ion channels as well as the SERT-related γ-aminobutyric acid- and glycine-transporters. Using 5-HT uptake assays, confocal microscopy and glutathione S-transferase (GST) pull-down assays we showed that Syn1A also interacts with SERT and alters the subcellular localization of the transporter, resulting in a reduction of 5-HT transport. In addition, we have used the yeast two-hybrid system to search for novel regulatory proteins that interact with the cytoplasmic N-terminal domain of SERT. By screening rat brain cDNA library we have identified six potential SERT-binding proteins. Here we also present progress towards the elucidation of the biological relevance of these proteins and their potential role for the regulation of the serotonin transporter.
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Conference Article|
November 01 2001
Regulation of the serotonin transporter by interacting proteins
J. Haase;
J. Haase
1
1Biochemistry Department, Trinity College, Dublin 2, Ireland
1To whom correspondence should be addressed (e-mail jhaase@tcd.ie).
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A.-M. Killian;
A.-M. Killian
1Biochemistry Department, Trinity College, Dublin 2, Ireland
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F. Magnani;
F. Magnani
1Biochemistry Department, Trinity College, Dublin 2, Ireland
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C. Williams
C. Williams
1Biochemistry Department, Trinity College, Dublin 2, Ireland
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Publisher: Portland Press Ltd
Received:
July 06 2001
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2001 Biochemical Society
2001
Biochem Soc Trans (2001) 29 (6): 722–728.
Article history
Received:
July 06 2001
Citation
J. Haase, A.-M. Killian, F. Magnani, C. Williams; Regulation of the serotonin transporter by interacting proteins. Biochem Soc Trans 1 November 2001; 29 (6): 722–728. doi: https://doi.org/10.1042/bst0290722
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