Evidence map›Paper›PMID 27011730›Full record

ArticleMolecular vision2016

Targeting of exon VI-skipping human RGR-opsin to the plasma membrane of pigment epithelium and co-localization with terminal complement complex C5b-9.

Harold Kochounian, Zhaoxia Zhang, Christine Spee, David R Hinton, Henry K W Fong

Abstract read
PubMed Full text at PMC
In one paragraph

Article in Molecular vision, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact, top 100% 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

5 citing papers in PubMed, 0 citations in OpenAlex.

  1. Retinal G-protein-coupled receptor deletion exacerbates AMD-like changes via the PINK1-parkin pathway under oxidative stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
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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

5 authors at 2 institutions in 1 country.

Harold KochounianDoheny Eye Institute, Los Angeles, CA.
Zhaoxia ZhangDepartment of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA; USC Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA.
Christine SpeeDepartment of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA.
David R HintonDepartment of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA; Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA; USC Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA.
Henry K W FongDepartment of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA; Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California, Los Angeles, CA; USC Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA.
Doheny Eye Institute · USUniversity of Southern California · US

Funding

VISION RESEARCHP30EY003040 · NEI · DOHENY EYE INSTITUTE · PI SUN, DEMING · 1985 to 2013
$7.0M
EXPERIMENTAL APPROACH TO MACULOPATHYR01EY001545 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HINTON, DAVID R. · 1985 to 2016
$6.0M
OPSINS, G PROTEIN PATHWAYS AND REGULATION IN RPE CELLSR01EY008364 · NEI · DOHENY EYE INSTITUTE · PI FONG, HENRY K · 1990 to 2006
$2.5M
NEI NIH HHS P30 EY003040NEI NIH HHS P30EY03040NEI NIH HHS R01 EY001545NEI NIH HHS R01 EY008364NEI NIH HHS R01EY01545NEI NIH HHS R01EY08364
6 · The paper itself

Abstract

purposeRare mutations in the human RGR gene lead to autosomal recessive retinitis pigmentosa or dominantly inherited peripapillary choroidal atrophy. Here, we analyze a common exon-skipping isoform of the human retinal G protein-coupled receptor opsin (RGR-d) to determine differences in subcellular targeting between RGR-d and normal RGR and possible association with abnormal traits in the human eye.

methodsThe terminal complement complex (C5b-9), vitronectin, CD46, syntaxin-4, and RGR-d were analyzed in human eye tissue from young and old donors or in cultured fetal RPE cells by means of immunofluorescent labeling and high-resolution confocal microscopy or immunohistochemical staining.

resultsWe observed that RGR-d is targeted to the basolateral plasma membrane of the RPE. RGR-d, but not normal RGR, is expressed in cultured human fetal RPE cells in which the protein also trafficks to the plasma membrane. In young donors, the amount of RGR-d protein in the basolateral plasma membrane was much higher than that in the RPE cells of older subjects. In older donor eyes, the level of immunoreactive RGR-d within RPE cells was often low or undetectable, and immunostaining of RGR-d was consistently strongest in extracellular deposits in Bruch's membrane. Double immunofluorescent labeling in the basal deposits revealed significant aggregate and small punctate co-localization of RGR-d with C5b-9 and vitronectin.

conclusionsRGR-d may escape endoplasmic reticulum-associated degradation and in contrast to full-length RGR, traffick to the basolateral plasma membrane, particularly in younger subjects. RGR-d in the plasma membrane indicates that the protein is properly folded, as misfolded membrane proteins cannot otherwise sort to the plasma membrane. The close association of extracellular RGR-d with both vitronectin and C5b-9 suggests a potential role of RGR-d-containing deposits in complement activation.

Indexed as

AgedAlternative SplicingBlotting, WesternBruch MembraneCell MembraneCells, CulturedComplement Membrane Attack ComplexExonsEye ProteinsFemaleFluorescent Antibody Technique, IndirectGenetic VectorsHumansMaleMembrane Cofactor ProteinMicroscopy, ConfocalCD46 protein, humanComplement Membrane Attack ComplexEye ProteinsG protein-coupled receptor RGRMembrane Cofactor ProteinOpsinsReceptors, G-Protein-CoupledRNA, MessengerVitronectin

Identifiers

PMID27011730
PMCPMC4783578
OpenAlexW27011730

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.