Regulation of the serotonin transporter by interacting proteins. (November 2001)

• Record Type: Journal Article
• Authors: Haase, J.; Killian, A.-M.; Magnani, F.; Williams, C.
• Is Part Of: Biochemical Society transactions. Volume 29:Number 6(2001)
• Page Start: 722
• Page End: 728
• Publication Date: 2001-11
• Subjects: neurotransmitter transporter -- protein trafficking -- protein-protein interactions; CLIP, cytoplasmic linker protein -- CLASP, CLIP-associated protein -- GABA, γ-aminobutync acid -- GAT, GABA transporter -- GLYT, glycine transporter -- GST, glutathione S-transferase -- 5-HT, 5-hydroxytryptamine -- NSERT, N-terminal domain of SERT -- PKC, protein kinase C -- SERT, serotonin transporter -- STBP, serotonin transporter binding protein -- SynIA, syntaxin IA -- TMH, transmembrane helix; Biochemistry -- Congresses; 572
• DOI: 10.1042/bst0290722
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : 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.