Evidence map›Paper›PMID 17913921›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007

Serotonin transporter phosphorylation by cGMP-dependent protein kinase is altered by a mutation associated with obsessive compulsive disorder.

Yuan-Wei Zhang, Joan Gesmonde, Sammanda Ramamoorthy, Gary Rudnick

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
6.2field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
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  6. microPublication biology · 2022
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  13. Review
  14. Control of serotonin transporter phosphorylation by conformational state.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  15. Common and rare alleles of the serotonin transporter gene, SLC6A4, associated with Tourette's disorder.Movement disorders : official journal of the Movement Disorder Society · 2013
    Article
  16. Article
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  18. Article
  19. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Yuan-Wei ZhangDepartment of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Joan Gesmonde
Sammanda Ramamoorthy
Gary Rudnick
Yale University · USMedical University of South Carolina · US

Funding

NEUROTRANSMITTER TRANSPORTR01DA008213 · NIDA · YALE UNIVERSITY · PI RUDNICK, GARY W · 1993 to 2014
$3.5M
Serotonin Transporter PhosphorylationR01MH062612 · NIMH · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAMAMOORTHY, SAMMANDA · 2002 to 2011
$2.4M
NIDA NIH HHS DA008213NIDA NIH HHS R01 DA008213NIMH NIH HHS MH62612NIMH NIH HHS R01 MH062612
6 · The paper itself

Abstract

Human serotonin transporter (hSERT) activity expressed in HeLa cells was stimulated by agents that release nitric oxide, stimulate soluble guanylyl cyclase, or activate cGMP-dependent protein kinase (PKG). This stimulation was blocked by a PKG inhibitor. A naturally occurring mutation, I425V, associated with obsessive-compulsive disorder and other neuropsychiatric disorders, activated hSERT and eliminated stimulation via the PKG pathway. Inhibitors of soluble guanylyl cyclase or PKG decreased activity of the I425V mutant, but not wild type, indicating that both wild-type and mutant transporters could exist in both high and low activity forms. Mutation of Thr-276 in the fifth transmembrane domain (TM5) to alanine or aspartate prevented activation of wild-type hSERT through the PKG pathway and also blocked the inhibition of I425V activity by inhibitors of the pathway. The accessibility of positions in TM5 near Thr-276 was modified in T276D, but not in I425V. These results are consistent with the hypothesis that PKG phosphorylates hSERT at Thr-276 and increases its activity by modifying the substrate permeation pathway formed, in part, by TM5. The effect of the I425V mutation may shift the balance of hSERT toward the phosphorylated form, possibly by interfering with the action of a phosphatase. However, association of hSERT with protein phosphatase 2A was not decreased in the I425V mutant.

Indexed as

MutationBiotinylationCell Adhesion MoleculesCyclic GMPCyclic GMP-Dependent Protein KinasesDose-Response Relationship, DrugDrug InteractionsEnzyme ActivationEnzyme InhibitorsHeLa CellsHumansImmunoprecipitationMicrofilament ProteinsMutagenesis, Site-DirectedNitric Oxide DonorsPenicillamine8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate8-bromoguanosino-3',5'-cyclic monophosphorothioateCell Adhesion MoleculesCyclic GMPCyclic GMP-Dependent Protein KinasesEnzyme InhibitorsMicrofilament ProteinsNitric Oxide DonorsPenicillaminePhosphoproteinsSerotoninSerotonin Plasma Membrane Transport ProteinsS-nitro-N-acetylpenicillamineThionucleotidesVasodilator-Stimulated Phosphoprotein

Identifiers

PMID17913921
PMCPMC6672823
OpenAlexW2010248207

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.