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Loss of PRCD alters number and packaging density of rhodopsin in rod photoreceptor disc membranes.

Abstract：

:Progressive rod-cone degeneration (PRCD) is a small protein localized to photoreceptor outer segment (OS) disc membranes. Several mutations in PRCD are linked to retinitis pigmentosa (RP) in canines and humans, and while recent studies have established that PRCD is required for high fidelity disc morphogenesis, its precise role in this process remains a mystery. To better understand the part which PRCD plays in disease progression as well as its contribution to photoreceptor OS disc morphogenesis, we generated a Prcd-KO animal model using CRISPR/Cas9. Loss of PRCD from the retina results in reduced visual function accompanied by slow rod photoreceptor degeneration. We observed a significant decrease in rhodopsin levels in Prcd-KO retina prior to photoreceptor degeneration. Furthermore, ultrastructural analysis demonstrates that rod photoreceptors lacking PRCD display disoriented and dysmorphic OS disc membranes. Strikingly, atomic force microscopy reveals that many disc membranes in Prcd-KO rod photoreceptor neurons are irregular, containing fewer rhodopsin molecules and decreased rhodopsin packing density compared to wild-type discs. This study strongly suggests an important role for PRCD in regulation of rhodopsin incorporation and packaging density into disc membranes, a process which, when dysregulated, likely gives rise to the visual defects observed in patients with PRCD-associated RP.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Sechrest ER,Murphy J,Senapati S,Goldberg AFX,Park PS,Kolandaivelu S

doi

10.1038/s41598-020-74628-2

subject

Has Abstract

pub_date

2020-10-21 00:00:00

pages

17885

issue

1

issn

2045-2322

pii

10.1038/s41598-020-74628-2

journal_volume

10

pub_type

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