ArticleThe Journal of biological chemistry2011
The serotonin transporter is an exclusive client of the coat protein complex II (COPII) component SEC24C.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 84 citations in OpenAlex.
- BRAP maintains SEC24D stability to regulate ER stress and promote cervical adenocarcinoma progression.Journal of translational medicine · 2026Article
- Optogenetic Regulation of Localization and Function of Serotonin Transporter by Modulating Its Interaction with Soluble Guanylate Cyclase.International journal of molecular sciences · 2026Article
- Regulation of Dopamine Transporter Surface Expression.Advances in neurobiology · 2025Review
- Nlp-dependent ER-to-Golgi transport.International journal of biological sciences · 2024Article
- Deficiency of Perry syndrome-associated p150NPJ Parkinson's disease · 2023Article
- Cargo selection in endoplasmic reticulum-to-Golgi transport and relevant diseases.The Journal of clinical investigation · 2023Review
- Article
- Murine SEC24D can substitute functionally for SEC24C during embryonic development.Scientific reports · 2021Article
- Functional and Biochemical Consequences of Disease Variants in Neurotransmitter Transporters: A Special Emphasis on Folding and Trafficking Deficits.Pharmacology & therapeutics · 2021Review
- SLC6 transporter oligomerization.Journal of neurochemistry · 2021Review
- Dynamic control of the dopamine transporter in neurotransmission and homeostasis.NPJ Parkinson's disease · 2021Review
- Proteomic Response of Rat Pituitary Under Chronic Mild Stress Reveals Insights Into Vulnerability and Resistance to Anxiety or Depression.Frontiers in genetics · 2021Article
- Review
- The Creatine Transporter Unfolded: A Knotty Premise in the Cerebral Creatine Deficiency Syndrome.Frontiers in synaptic neuroscience · 2020Review
- Article
- Btbd3 expression regulates compulsive-like and exploratory behaviors in mice.Translational psychiatry · 2019Article
- How to rescue misfolded SERT, DAT and NET: targeting conformational intermediates with atypical inhibitors and partial releasers.Biochemical Society transactions · 2019Review
- Dopamine transporter forms stable dimers in the live cell plasma membrane in a phosphatidylinositol 4,5-bisphosphate-independent manner.The Journal of biological chemistry · 2019Article
- Trafficking of the amino acid transporter BBiochimica et biophysica acta. Molecular cell research · 2019Article
- The COPII cargo adapter SEC24C is essential for neuronal homeostasis.The Journal of clinical investigation · 2018Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transporters for serotonin (SERT), dopamine, and noradrenaline have a conserved hydrophobic core but divergent N and C termini. The C terminus harbors the binding site for the coat protein complex II (COPII) cargo-binding protein SEC24. Here we explored which SEC24 isoform was required for export of SERT from the endoplasmic reticulum (ER). Three lines of evidence argue that SERT can only exit the ER by recruiting SEC24C: (i) Mass spectrometry showed that a peptide corresponding to the C terminus of SERT recruited SEC24C-containing COPII complexes from mouse brain lysates. (ii) Depletion of individual SEC24 isoforms by siRNAs revealed that SERT was trapped in the ER only if SEC24C was down-regulated, in both, cells that expressed SERT endogenously or after transfection. The combination of all siRNAs was not more effective than that directed against SEC24C. A SERT mutant in which the SEC24C-binding motif ((607)RI(608)) was replaced by alanine was insensitive to down-regulation of SEC24C levels. (iii) Overexpression of a SEC24C variant with a mutation in the candidate cargo-binding motif (SEC24C-D796V/D797N) but not of the corresponding mutant SEC24D-D733V/D734N reduced SERT surface levels. In contrast, noradrenaline and dopamine transporters and the more distantly related GABA transporter 1 relied on SEC24D for ER export. These observations demonstrate that closely related transporters are exclusive client cargo proteins for different SEC24 isoforms. The short promoter polymorphism results in reduced SERT cell surface levels and renders affected individuals more susceptible to depression. By inference, variations in the Sec24C gene may also affect SERT cell surface levels and thus be linked to mood disorders.
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