ArticleThe Journal of biological chemistry2014
A cytosolic relay of heat shock proteins HSP70-1A and HSP90β monitors the folding trajectory of the serotonin transporter.
Article in The Journal of biological chemistry, 2014. 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.
- Deciphering Ibogaine's Matrix Pharmacology: Multiple Transporter Modulation at Serotonin Synapses.Journal of the American Chemical Society · 2026Article
- Pharmacological Evaluation of Tropane Analogues at the Serotonin Transporter.ACS chemical neuroscience · 2025Article
- Unifying perspectives on the activity and genotypic targeting of pharmacological chaperones.The Journal of biological chemistry · 2025Review
- Pathogenic variants at the N-terminal arginine residue 44 disrupt human GABA transporter 1 function: insights fromFrontiers in pharmacology · 2025Article
- Hyperthermia and targeting heat shock proteins: innovative approaches for neurodegenerative disorders and Long COVID.Frontiers in neuroscience · 2025Review
- SMR peptide antagonizesMicrobiology spectrum · 2024Article
- A transporter's doom or destiny:Frontiers in molecular neuroscience · 2024Review
- Effect of lairage time prior to slaughter on stress in pigs: a path analysis.Porcine health management · 2023Article
- The cell cycle protein MAD2 facilitates endocytosis of the serotonin transporter in the neuronal soma.EMBO reports · 2023Article
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- Article
- Molecular and Clinical Repercussions of GABA Transporter 1 Variants Gone Amiss: Links to Epilepsy and Developmental Spectrum Disorders.Frontiers in molecular biosciences · 2022Review
- Article
- Functional and Biochemical Consequences of Disease Variants in Neurotransmitter Transporters: A Special Emphasis on Folding and Trafficking Deficits.Pharmacology & therapeutics · 2021Review
- Tropane-Based Ibogaine Analog Rescues Folding-Deficient Serotonin and Dopamine Transporters.ACS pharmacology & translational science · 2021Article
- The Creatine Transporter Unfolded: A Knotty Premise in the Cerebral Creatine Deficiency Syndrome.Frontiers in synaptic neuroscience · 2020Review
- Amino Acid Transporter SLC6A14 (ATBFrontiers in cell and developmental biology · 2020Review
- Structures of Hsp90α and Hsp90β bound to a purine-scaffold inhibitor reveal an exploitable residue for drug selectivity.Proteins · 2019Article
- Functional and structural analysis of rare SLC2A2 variants associated with Fanconi-Bickel syndrome and metabolic traits.Human mutation · 2019Article
- How to rescue misfolded SERT, DAT and NET: targeting conformational intermediates with atypical inhibitors and partial releasers.Biochemical Society transactions · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the C terminus of the serotonin transporter (SERT) disrupt folding and export from the endoplasmic reticulum. Here we examined the hypothesis that a cytosolic heat shock protein relay was recruited to the C terminus to assist folding of SERT. This conjecture was verified by the following observations. (i) The proximal portion of the SERT C terminus conforms to a canonical binding site for DnaK/heat shock protein of 70 kDa (HSP70). A peptide covering this segment stimulated ATPase activity of purified HSP70-1A. (ii) A GST fusion protein comprising the C terminus of SERT pulled down HSP70-1A. The interaction between HSP70-1A and SERT was visualized in live cells by Förster resonance energy transfer: it was restricted to endoplasmic reticulum-resident transporters and enhanced by an inhibitor that traps HSP70-1A in its closed state. (iv) Co-immunoprecipitation confirmed complex formation of SERT with HSP70-1A and HSP90β. Consistent with an HSP relay, co-chaperones (e.g. HSC70-HSP90-organizing protein) were co-immunoprecipitated with the stalled mutants SERT-R607A/I608A and SERT-P601A/G602A. (v) Depletion of HSP90β by siRNA or its inhibition increased the cell surface expression of wild type SERT and SERT-F604Q. In contrast, SERT-R607A/I608A and SERT-P601A/G602A were only rendered susceptible to inhibition of HSP70 and HSP90 by concomitant pharmacochaperoning with noribogaine. (vi) In JAR cells, inhibition of HSP90 also increased the levels of SERT, indicating that endogenously expressed transporter was also susceptible to control by HSP90β. These findings support the concept that the folding trajectory of SERT is sampled by a cytoplasmic chaperone relay.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.