Evidence map›Paper›PMID 23966685›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013

Signals governing the trafficking and mistrafficking of a ciliary GPCR, rhodopsin.

Kerrie H Lodowski, Richard Lee, Philip Ropelewski, Ina Nemet, Guilian Tian, Yoshikazu Imanishi

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

44 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Systematic review:Frontiers in medicine · 2025
    Review
  6. Contribution of intraflagellar transport to compartmentalization and maintenance of the photoreceptor cell.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  7. Rhodopsin mislocalization drives ciliary dysregulation in a novel autosomal dominant retinitis pigmentosa knock-in mouse model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Comparison of Ciliary Targeting of Two Rhodopsin-Like GPCRs: Role of C-Terminal Localization Sequences in Relation to Cilium Type.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  13. Functional compartmentalization of photoreceptor neurons.Pflugers Archiv : European journal of physiology · 2021
    Review
  14. Compartmentalization of Photoreceptor Sensory Cilia.Frontiers in cell and developmental biology · 2021
    Review
  15. Review
  16. Article
  17. Article
  18. Disrupted Plasma Membrane Protein Homeostasis in aThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019
    Article
  19. Review
  20. Antagonistic regulation of trafficking toProceedings of the National Academy of Sciences of the United States of America · 2018
    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 1 institution in 1 country.

Kerrie H LodowskiDepartment of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Richard Lee
Philip Ropelewski
Ina Nemet
Guilian Tian
Yoshikazu Imanishi
Case Western Reserve University · US

Funding

TISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Irina A Pikuleva · 1997 to 2026
$17.7M
VISUAL SCIENCES TRAINING PROGRAMT32EY007157 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Johannes Friedrich von Lintig · 2000 to 2026
$5.5M
TRAINING IN METABOLISMT32DK007319 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI BRUNENGRABER, HENRI · 1986 to 2013
$5.0M
Illuminating the process of rod outer segment morphogenesisR01EY020826 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI IMANISHI, YOSHIKAZU · 2010 to 2013
$1.4M
NEI NIH HHS EY011373NEI NIH HHS EY020826NEI NIH HHS P30 EY011373NEI NIH HHS R01 EY020826NEI NIH HHS T32 EY007157NIDDK NIH HHS DK007319NIDDK NIH HHS T32 DK007319
6 · The paper itself

Abstract

Rhodopsin is a cilia-specific GPCR essential for vision. Rhodopsin mislocalization is associated with blinding diseases called retinal ciliopathies. The mechanism by which rhodopsin mislocalizes in rod photoreceptor neurons is not well understood. Therefore, we investigated the roles of trafficking signals in rhodopsin mislocalization. Rhodopsin and its truncation mutants were fused to a photoconvertible fluorescent protein, Dendra2, and expressed in Xenopus laevis rod photoreceptors. Photoconversion of Dendra2 causes a color change from green to red, enabling visualization of the dynamic events associated with rhodopsin trafficking and renewal. We found that rhodopsin mislocalization is a facilitated process for which a signal located within 322-326 aa (CCGKN) is essential. An additional signal within 327-336 aa further facilitated the mislocalization. This collective mistrafficking signal confers toxicity to rhodopsin and causes mislocalization when the VXPX cilia-targeting motif is absent. We also determined that the VXPX motif neutralizes this mistrafficking signal, enhances ciliary targeting at least 10-fold, and accelerates trafficking of post-Golgi vesicular structures. In the absence of the VXPX motif, mislocalized rhodopsin is actively cleared through secretion of vesicles into the extracellular milieu. Therefore, this study unveiled the multiple roles of trafficking signals in rhodopsin localization and renewal.

Indexed as

Amino Acid SequenceAnimalsAnimals, Genetically ModifiedAnuraEyeFemaleGene Expression RegulationLuminescent ProteinsMaleModels, MolecularMutationOrgan Culture TechniquesPhotic StimulationProtein BindingProtein Structure, TertiaryProtein TransportLuminescent ProteinsReceptors, G-Protein-CoupledRhodopsinSodium-Potassium-Exchanging ATPase

Identifiers

PMID23966685
PMCPMC3755712
OpenAlexW2119960283

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.