Type

Journal Article

Authors

Gudrun Ahnert-Hilger
Johannes-Friedrich Zander
Zohreh Farsi
Kieran Wynne
Elysian Chow
Agnieszka Münster-Wandowski
Heidi Kaastrup Müller
Joanna Grudzinska-Goebel
Jana Haase

Subjects

Biochemistry

Topics
protein complexes mitochondrial membranes proteins serotonin site specific high affinity energy metabolism yeast two hybrid

Serotonin Transporter Associated Protein Complexes Are Enriched in Synaptic Vesicle Proteins and Proteins Involved in Energy Metabolism and Ion Homeostasis. (2017)

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.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Gudrun Ahnert-Hilger, Johannes-Friedrich Zander, Zohreh Farsi, Kieran Wynne, Elysian Chow, Agnieszka Münster-Wandowski, Heidi Kaastrup Müller, Joanna Grudzinska-Goebel, Jana Haase

Experts in our system

1
Kieran Wynne
Royal College of Surgeons in Ireland
Total Publications: 45
 
2
Jana Haase
University College Dublin
Total Publications: 7