Evidence map›Paper›PMID 21928830›Full record

ArticleBiochemistry2011

Retinal degeneration 3 (RD3) protein inhibits catalytic activity of retinal membrane guanylyl cyclase (RetGC) and its stimulation by activating proteins.

Igor V Peshenko, Elena V Olshevskaya, Seifollah Azadi, Laurie L Molday, Robert S Molday, Alexander M Dizhoor

Abstract read
In one paragraph

Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

34 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Article
  3. Development of an AAV-CRISPR-Cas9-based treatment for dominant cone-rod dystrophy 6.Molecular therapy. Methods & clinical development · 2023
    Article
  4. Article
  5. Review
  6. Review
  7. The Journal of biological chemistry · 2020
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Photoreceptor Guanylate Cyclase (Frontiers in molecular neuroscience · 2018
    Article
  16. Article
  17. Article
  18. Article
  19. 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

6 authors at 2 institutions in 2 countries.

Igor V PeshenkoDepartment of Basic Sciences and Pennsylvania College of Optometry, Salus University, Elkins Park, Pennsylvania 19027, United States.
Elena V Olshevskaya
Seifollah Azadi
Laurie L Molday
Robert S Molday
Alexander M Dizhoor
Salus University · USUniversity of British Columbia · CA

Funding

REGULATION OF CYCLIC GMP SYNTHESIS IN PHOTORECEPTORSR01EY011522 · NEI · WAYNE STATE UNIVERSITY · PI ALEXANDER M DIZHOOR · 1996 to 2026
$9.9M
STRUCTURE/FUNCTION OF ROS PLASMA MEMBRANE PROTEINSR01EY002422 · NEI · UNIVERSITY OF BRITISH COLUMBIA · PI MOLDAY, ROBERT S · 1985 to 2017
$3.5M
NEI NIH HHS EY02422NEI NIH HHS EY11522NEI NIH HHS R01 EY002422NEI NIH HHS R01 EY011522
6 · The paper itself

Abstract

Retinal membrane guanylyl cyclase (RetGC) in the outer segments of vertebrate photoreceptors is controlled by guanylyl cyclase activating proteins (GCAPs), responding to light-dependent changes of the intracellular Ca(2+) concentrations. We present evidence that a different RetGC binding protein, retinal degeneration 3 protein (RD3), is a high-affinity allosteric modulator of the cyclase which inhibits RetGC activity at submicromolar concentrations. It suppresses the basal activity of RetGC in the absence of GCAPs in a noncompetitive manner, and it inhibits the GCAP-stimulated RetGC at low intracellular Ca(2+) levels. RD3 opposes the allosteric activation of the cyclase by GCAP but does not significantly change Ca(2+) sensitivity of the GCAP-dependent regulation. We have tested a number of mutations in RD3 implicated in human retinal degenerative disorders and have found that several mutations prevent the stable expression of RD3 in HEK293 cells and decrease the affinity of RD3 for RetGC1. The RD3 mutant lacking the carboxy-terminal half of the protein and associated with Leber congenital amaurosis type 12 (LCA12) is unable to suppress the activity of the RetGC1/GCAP complex. Furthermore, the inhibitory activity of the G57V mutant implicated in cone-rod degeneration is strongly reduced. Our results suggest that inhibition of RetGC by RD3 may be utilized by photoreceptors to block RetGC activity during its maturation and/or incorporation into the photoreceptor outer segment rather than participate in dynamic regulation of the cyclase by Ca(2+) and GCAPs.

Indexed as

AnimalsBinding, CompetitiveCatalysisCodon, NonsenseEye ProteinsGuanylate CyclaseGuanylate Cyclase-Activating ProteinsHEK293 CellsHumansMembrane ProteinsMiceMutation, MissenseNuclear ProteinsProtein BindingReceptors, Cell SurfaceRecombinant ProteinsCodon, NonsenseEye ProteinsGuanylate Cyclaseguanylate cyclase 1Guanylate Cyclase-Activating ProteinsMembrane ProteinsNuclear ProteinsRD3 protein, humanReceptors, Cell SurfaceRecombinant Proteinsretinal degeneration 3 protein, mouse

Identifiers

PMID21928830
PMCPMC3206180
OpenAlexW2048595956

What OpenQuestion holds

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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.