Evidence map›Paper›PMID 23555781›Full record

ArticlePloS one2013

Inhibition of dopamine transporter activity by G protein βγ subunits.

Jennie Garcia-Olivares, Delany Torres-Salazar, William A Owens, Tracy Baust, David P Siderovski, Susan G Amara, Jun Zhu, Lynette C Daws, Gonzalo E Torres

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

23 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Article
  3. Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology.Advances in experimental medicine and biology · 2021
    Review
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  14. Article
  15. Article
  16. Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA methylation in VIPR2.Journal of child psychology and psychiatry, and allied disciplines · 2016
    Article
  17. Article
  18. Article
  19. Muscarinic regulation of dopamine and glutamate transmission in the nucleus accumbens.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  20. Article
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

9 authors at 4 institutions in 1 country.

Jennie Garcia-OlivaresDepartment of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Delany Torres-Salazar
William A Owens
Tracy Baust
David P Siderovski
Susan G Amara
Jun Zhu
Lynette C Daws
Gonzalo E Torres
University of Pittsburgh · USThe University of Texas Health Science Center at San Antonio · USUniversity of North Carolina at Chapel Hill · USUniversity of South Carolina · US

Funding

Structure, Function and Pharmacology of Neurotransmitter Reuptake SystemsZIAMH002946 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI AMARA, SUSAN · 2013 to 2025
$26.6M
Proteomic/Genetic Approaches to Monoamine TransportersK01DA016710 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TORRES, GONZALO E. · 2003 to 2007
$765k
NIDA NIH HHS DA 016710-02NIDA NIH HHS K01 DA016710
6 · The paper itself

Abstract

Uptake through the Dopamine Transporter (DAT) is the primary mechanism of terminating dopamine signaling within the brain, thus playing an essential role in neuronal homeostasis. Deregulation of DAT function has been linked to several neurological and psychiatric disorders including ADHD, schizophrenia, Parkinson's disease, and drug addiction. Over the last 15 years, several studies have revealed a plethora of mechanisms influencing the activity and cellular distribution of DAT; suggesting that fine-tuning of dopamine homeostasis occurs via an elaborate interplay of multiple pathways. Here, we show for the first time that the βγ subunits of G proteins regulate DAT activity. In heterologous cells and brain tissue, a physical association between Gβγ subunits and DAT was demonstrated by co-immunoprecipitation. Furthermore, in vitro pull-down assays using purified proteins established that this association occurs via a direct interaction between the intracellular carboxy-terminus of DAT and Gβγ. Functional assays performed in the presence of the non-hydrolyzable GTP analog GTP-γ-S, Gβγ subunit overexpression, or the Gβγ activator mSIRK all resulted in rapid inhibition of DAT activity in heterologous systems. Gβγ activation by mSIRK also inhibited dopamine uptake in brain synaptosomes and dopamine clearance from mouse striatum as measured by high-speed chronoamperometry in vivo. Gβγ subunits are intracellular signaling molecules that regulate a multitude of physiological processes through interactions with enzymes and ion channels. Our findings add neurotransmitter transporters to the growing list of molecules regulated by G-proteins and suggest a novel role for Gβγ signaling in the control of dopamine homeostasis.

Indexed as

AnimalsBiotinylationBrainCorpus StriatumDopamineDopamine Plasma Membrane Transport ProteinsGlutathione TransferaseGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsGuanosine TriphosphateHEK293 CellsHomeostasisHumansImmunoprecipitationMiceMice, Inbred C57BLDopamineDopamine Plasma Membrane Transport ProteinsGlutathione TransferaseG-protein Beta gammaGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsGuanosine Triphosphate

Identifiers

PMID23555781
PMCPMC3608556
OpenAlexW2062594688

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.