Evidence map›Paper›PMID 26169958›Full record

ArticleCellular signalling2015

Dopamine receptor D4 internalization requires a beta-arrestin and a visual arrestin.

Janise D Deming, Jung-A Shin, Kayleen Lim, Eun-Jin Lee, Kathleen Van Craenenbroeck, Cheryl Mae Craft

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular signalling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Visual Cone Arrestin 4 Contributes to Visual Function and Cone Health.Investigative ophthalmology & visual science · 2015
    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

6 authors at 3 institutions in 3 countries.

Janise D DemingMary D. Allen Laboratory for Vision Research, USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, 2250 Alcazar Street, Clinical Science Annex 215, Los Angeles, CA 90033, USA. Electronic address: Janise.deming@gmail.com.
Jung-A ShinMary D. Allen Laboratory for Vision Research, USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, 2250 Alcazar Street, Clinical Science Annex 215, Los Angeles, CA 90033, USA; Department of Anatomy, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea. Electronic address: sja@ewha.ac.kr.
Kayleen LimMary D. Allen Laboratory for Vision Research, USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, 2250 Alcazar Street, Clinical Science Annex 215, Los Angeles, CA 90033, USA. Electronic address: kaylim13@gmail.com.
Eun-Jin LeeMary D. Allen Laboratory for Vision Research, USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, 2250 Alcazar Street, Clinical Science Annex 215, Los Angeles, CA 90033, USA; Department of Biomedical Engineering, University of Southern California Viterbi School of Engineering, 1042 Downey Way, Los Angeles, CA 90089-1111, USA. Electronic address: eunjinl@usc.edu.
Kathleen Van CraenenbroeckLaboratory of GPCR Expression and Signal Transduction (L-GEST), Ghent University-UGent, K.L. Ledeganckstraat 35, B-9000 Gent, Belgium. Electronic address: kathleen.vancraenenbroeck@ugent.be.
Cheryl Mae CraftMary D. Allen Laboratory for Vision Research, USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, 2250 Alcazar Street, Clinical Science Annex 215, Los Angeles, CA 90033, USA; Department of Cell & Neurobiology, Keck School of Medicine of the University of Southern California, 2250 Alcazar Street, Clinical Science Center 135H, Los Angeles, CA 90033, USA. Electronic address: CherylMae.Craft@med.usc.edu.
University of Southern California · USEwha Womans University · KRGhent University · BE

Funding

VISION RESEARCHP30EY003040 · NEI · DOHENY EYE INSTITUTE · PI SUN, DEMING · 1985 to 2013
$7.0M
Mechanisms of Cone Pigment DeactivationR01EY015851 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CRAFT, CHERYL MAE · 2005 to 2009
$1.8M
NEI NIH HHS EY015851NEI NIH HHS EY03040NEI NIH HHS P30 EY003040NEI NIH HHS R01 EY015851
6 · The paper itself

Abstract

purposeThe G-protein coupled receptor (GPCR) Dopamine Receptor D4 (DRD4) plays an essential role in cAMP regulation and gap junctional coupling in the photoreceptors, where DRD4 expression is under circadian control. Previous in vitro transfection studies of human DRD4 desensitization have reported that DRD4 is not internalized upon dopamine stimulation when beta-arrestin is co-transfected with DRD4. We hypothesized that the visual arrestins, ARR1 and ARR4, play a modulatory role in DRD4 desensitization in the photoreceptors.

methodsTo test this hypothesis, immunohistochemistry analysis of mouse retinas was used to determine the cellular localization of beta-arrestins and DRD4 in photoreceptors. In vitro studies were performed in HEK293T cells transiently transfected with human DRD4 and arrestins. First, co-immunoprecipitation experiments were executed to test protein-protein interactions and to investigate the effect of dopamine stimulation. Second, immunohistochemistry analysis was implemented to study DRD4 internalization and translocation of ARR4.

resultsImmunohistochemistry studies of mouse retinas confirmed the expression of beta-arrestin 2, ARR1 and ARR4, as well as DRD4 in mouse cone photoreceptor inner segments. Co-immunoprecipitation experiments revealed a dopamine-dependent protein-protein interaction between human DRD4 and ARR4. In vitro internalization experiments showed that no detectable internalization of DRD4 was observed with any single arrestin co-transfected. However, a dopamine-dependent internalization of DRD4 was observed with three out of six sets of two arrestins co-transfected with DRD4. Each of these pairs of arrestins contained one visual arrestin and one beta-arrestin, and no internalization was observed with either two visual arrestins or two beta-arrestins. Additional time-course experiments revealed that in vitro, ARR4 translocates to co-localize with DRD4 at the plasma membrane in response to 30min of dopamine stimulation.

conclusionsThe results have functional implications and we hypothesize that the desensitization and internalization of DRD4 in photoreceptors are synergistically mediated by both visual and beta-arrestins. These results are additionally unique because they demonstrate for the first time that at least one G-protein coupled receptor, DRD4, requires two arrestins for desensitization and internalization, and opens up the possibility that other G-protein coupled receptors may require more than one arrestin for desensitization and/or internalization.

Indexed as

AnimalsArrestinsbeta-Arrestin 1beta-Arrestin 2beta-ArrestinsCell MembraneHEK293 CellsHumansMice, Inbred C57BLMice, KnockoutProtein BindingProtein TransportReceptors, Dopamine D4RetinaARRB1 protein, humanArrb1 protein, mouseARRB2 protein, humanArrb2 protein, mousearrestin 4 protein, mouseArrestinsbeta-Arrestin 1beta-Arrestin 2beta-ArrestinsDrd4 protein, mouseReceptors, Dopamine D4Beta arrestinCone arrestinDopamine receptor D4PhotoreceptorRetinaVisual arrestin

Identifiers

PMID26169958
PMCPMC9112046
OpenAlexW887768225

What OpenQuestion holds

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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.