ArticleThe Journal of biological chemistry2013
Switching the clientele: a lysine residing in the C terminus of the serotonin transporter specifies its preference for the coat protein complex II component SEC24C.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- Optogenetic Regulation of Localization and Function of Serotonin Transporter by Modulating Its Interaction with Soluble Guanylate Cyclase.International journal of molecular sciences · 2026Article
- Mechanisms of COPII coat assembly and cargo recognition in the secretory pathway.Nature reviews. Molecular cell biology · 2025Review
- Nlp-dependent ER-to-Golgi transport.International journal of biological sciences · 2024Article
- Article
- 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
- The Amino Terminus of LeuT Changes Conformation in an Environment Sensitive Manner.Neurochemical research · 2020Article
- Amino Acid Transporter SLC6A14 (ATBFrontiers in cell and developmental biology · 2020Review
- The Creatine Transporter Unfolded: A Knotty Premise in the Cerebral Creatine Deficiency Syndrome.Frontiers in synaptic neuroscience · 2020Review
- Tales of tails in transporters.Open biology · 2019Review
- 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
- The carboxy-terminus, a key regulator of protein function.Critical reviews in biochemistry and molecular biology · 2019Review
- Trafficking of the amino acid transporter BBiochimica et biophysica acta. Molecular cell research · 2019Article
- Big Lessons from Tiny Flies:International journal of molecular sciences · 2018Review
- Dopamine transporter oligomerization involves the scaffold domain, but spares the bundle domain.PLoS computational biology · 2018Article
- Identification and characterization of the Fasciola hepatica sodium- and chloride-dependent taurine transporter.PLoS neglected tropical diseases · 2018Article
- Structural basis for recognition of diverse antidepressants by the human serotonin transporter.Nature structural & molecular biology · 2018Article
- Relax, Cool Down and Scaffold: How to Restore Surface Expression of Folding-Deficient Mutant GPCRs and SLC6 Transporters.International journal of molecular sciences · 2017Review
- An unfolding story: Small molecules remedy misfolded monoamine transporters.The international journal of biochemistry & cell biology · 2017Review
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serotonin transporter (SERT) maintains serotonergic neurotransmission via rapid reuptake of serotonin from the synaptic cleft. SERT relies exclusively on the coat protein complex II component SEC24C for endoplasmic reticulum (ER) export. The closely related transporters for noradrenaline and dopamine depend on SEC24D. Here, we show that discrimination between SEC24C and SEC24D is specified by the residue at position +2 downstream from the ER export motif ((607)RI(608) in SERT). Substituting Lys(610) with tyrosine, the corresponding residue found in the noradrenaline and dopamine transporters, switched the SEC24 isoform preference: SERT-K610Y relied solely on SEC24D to reach the cell surface. This analysis was extended to other SLC6 (solute carrier 6) transporter family members: siRNA-dependent depletion of SEC24C, but not of SEC24D, reduced surface levels of the glycine transporter-1a, the betaine/GABA transporter and the GABA transporter-4. Experiments with dominant negative versions of SEC24C and SEC24D recapitulated these findings. We also verified that the presence of two ER export motifs (in concatemers of SERT and GABA transporter-1) supported recruitment of both SEC24C and SEC24D. To the best of our knowledge, this is the first report to document a change in SEC24 specificity by mutation of a single residue in the client protein. Our observations allowed for deducing a rule for SLC6 family members: a hydrophobic residue (Tyr or Val) in the +2 position specifies interaction with SEC24D, and a hydrophilic residue (Lys, Asn, or Gln) recruits SEC24C. Variations in SEC24C are linked to neuropsychiatric disorders. The present findings provide a mechanistic explanation. Variations in SEC24C may translate into distinct surface levels of neurotransmitter transporters.
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