Evidence map›Paper›PMID 12682063›Full record

ArticleThe Journal of biological chemistry2003

The dopamine transporter constitutively internalizes and recycles in a protein kinase C-regulated manner in stably transfected PC12 cell lines.

Merewyn K Loder, Haley E Melikian

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed, 1 pooled it
7.6field-weighted citation impact, top 1% 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

120 citing papers in PubMed, 1 synthesis or guideline pooled it, 270 citations in OpenAlex.

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60 more citing papers are in PubMed but not listed here.

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

2 authors at 2 institutions in 1 country.

Merewyn K LoderBrudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts School of Medicine, 303 Belmont Street, Worcester, MA 01604, USA.
Haley E Melikian
Neuropsychiatric Research Institute · USUniversity of Massachusetts Chan Medical School · US

Funding

Trafficking and Regulation of Monoamine TransportersR01DA015169 · NIDA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MELIKIAN, HALEY E · 2002 to 2017
$5.2M
NIDA NIH HHS R01 DA015169NIDA NIH HHS R01 DA 15169-01
6 · The paper itself

Abstract

The dopamine transporter (DAT) removes dopamine from the extracellular milieu and is potently inhibited by number of psychoactive drugs, including cocaine, amphetamines, and methylphenidate (Ritalin). Multiple lines of evidence demonstrate that protein kinase C (PKC) down-regulates dopamine transport, primarily by redistributing DAT from the plasma membrane to endosomal compartments, although the mechanisms facilitating transporter sequestration are not defined. Here, we demonstrate that DAT constitutively internalizes and recycles in rat pheochromocytoma (PC12) cells. Temperature blockades demonstrated basal internalization and reliance on recycling to maintain DAT cell surface levels. In contrast, recycling blockade with bafilomycin A1 significantly decreased transferrin receptor (TfR) surface expression but had no effect on DAT surface levels, suggesting that DAT and TfR traffic via distinct endosomal mechanisms. Kinetic analyses reveal robust constitutive DAT cycling to and from the plasma membrane, independent of transporter expression levels. In contrast, phorbol ester-mediated PKC activation accelerated DAT endocytosis and attenuated transporter recycling in a manner sensitive to DAT expression levels. These data demonstrate constitutive DAT trafficking and that PKC-mediated DAT sequestration is achieved by a combination of accelerated internalization and reduced recycling. Additionally, the differential sensitivity to expression level exhibited by constitutive and regulated DAT trafficking suggests that these two processes are mediated by independent cellular mechanisms.

Indexed as

MacrolidesMembrane GlycoproteinsNerve Tissue ProteinsAnimalsAnti-Bacterial AgentsBiological TransportBiotinylationCell LineDopamine Plasma Membrane Transport ProteinsEndocytosisEnzyme ActivationHumansKineticsMembrane Transport ProteinsModels, BiologicalPC12 CellsAnti-Bacterial Agentsbafilomycin ADopamine Plasma Membrane Transport ProteinsMacrolidesMembrane GlycoproteinsMembrane Transport ProteinsNerve Tissue ProteinsProtein Kinase CSLC6A3 protein, humanSlc6a3 protein, rat

Identifiers

PMID12682063
PMCPMC2597781
OpenAlexW2093414544

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.