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  Serotonin transporter associated protein complexes are enriched in synaptic vesicle proteins and proteins involved in energy metabolism and ion homeostasis.

Haase, J., Grudzinska-Goebel, J., Müller, H. K., Münster-Wandowski, A., Chow, E., Wynne, K., et al. (2017). Serotonin transporter associated protein complexes are enriched in synaptic vesicle proteins and proteins involved in energy metabolism and ion homeostasis. ACS Chemical Neuroscience, 8(5), 1101-1116. doi:10.1021/acschemneuro.6b00437.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-6EDD-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-240D-9
Genre: Journal Article

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 Creators:
Haase, J., Author
Grudzinska-Goebel, J., Author
Müller, H. K., Author
Münster-Wandowski, A., Author
Chow, E., Author
Wynne, K., Author
Farsi, Z.1, Author              
Zander, J. F., Author
Ahnert-Hilger, G., Author
Affiliations:
1Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society, ou_578595              

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Free keywords: hippocampus; mitochondria; protein−protein interactions; proteomics; Serotonin transporter; synaptic vesicle
 Abstract: The serotonin transporter (SERT) mediates Na+-dependent high-affinity serotonin uptake and plays a key role in regulating extracellular serotonin concentration in the brain and periphery. To gain novel insight into SERT regulation, we conducted a comprehensive proteomics screen to identify components of SERT-associated protein complexes in the brain by employing three independent approaches. In vivo SERT complexes were purified from rat brain using an immobilized high-affinity SERT ligand, amino-methyl citalopram. This approach was combined with GST pulldown and yeast two-hybrid screens using N- and C-terminal cytoplasmic transporter domains as bait. Potential SERT associated proteins detected by at least two of the interaction methods were subjected to gene ontology analysis resulting in the identification of functional protein clusters that are enriched in SERT complexes. Prominent clusters include synaptic vesicle proteins, as well as proteins involved in energy metabolism and ion homeostasis. Using subcellular fractionation and electron microscopy we provide further evidence that SERT is indeed associated with synaptic vesicle fractions, and colocalizes with small vesicular structures in axons and axon terminals. We also show that SERT is found in close proximity to mitochondrial membranes in both, hippocampal and neocortical regions. We propose a model of the SERT interactome, in which SERT is distributed between different subcellular compartments through dynamic interactions with site-specific protein complexes. Finally, our protein interaction data suggest novel hypotheses for the regulation of SERT activity and trafficking, which ultimately impact on serotonergic neurotransmission and serotonin dependent brain functions.

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Language(s): eng - English
 Dates: 2017-03-31
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.1021/acschemneuro.6b00437
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Title: ACS Chemical Neuroscience
Source Genre: Journal
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Pages: - Volume / Issue: 8 (5) Sequence Number: - Start / End Page: 1101 - 1116 Identifier: -