Dataset Information

Light regulates the ciliary protein transport and outer segment disc renewal of mammalian photoreceptors.

ABSTRACT: The outer segment (OS) of the rod photoreceptor is a light-sensing cilium containing ~1,000 membrane-bound discs. Each day, discs constituting the distal tenth of the OS are shed, whereas nascent discs are formed at the base of the OS through the incorporation of molecules transported from the inner segment. The mechanisms regulating these processes remain elusive. Here, we show that rhodopsin preferentially enters the OS in the dark. Photoexcitation of post-Golgi rhodopsins retains them in the inner segment. Disc-rim protein peripherin2/rds enters the OS following a rhythm complementary to that of rhodopsin. Light-dark cycle-regulated protein trafficking serves as a mechanism to segregate rhodopsin-rich and peripherin2/rds-rich discs into alternating stacks, which are flanked by characteristic cytoplasmic pockets. This periodic cytostructure divides the OS into approximately ten fractions, each containing discs synthesized in a single day. This mechanism may explain how the rod photoreceptor balances the quantity of discs added and removed daily.

SUBMITTER: Hsu YC

PROVIDER: S-EPMC4374123 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Light regulates the ciliary protein transport and outer segment disc renewal of mammalian photoreceptors.

Hsu Ya-Chu YC Chuang Jen-Zen JZ Sung Ching-Hwa CH

Developmental cell 20150301 6

The outer segment (OS) of the rod photoreceptor is a light-sensing cilium containing ~1,000 membrane-bound discs. Each day, discs constituting the distal tenth of the OS are shed, whereas nascent discs are formed at the base of the OS through the incorporation of molecules transported from the inner segment. The mechanisms regulating these processes remain elusive. Here, we show that rhodopsin preferentially enters the OS in the dark. Photoexcitation of post-Golgi rhodopsins retains them in the ...[more]

PMID: 25805137

Similar Datasets

Project description:C8ORF37 is a causative gene for three different clinical forms of incurable retinal degeneration. However, the completely unknown function of C8ORF37 limits our understanding of the pathogenicity of C8ORF37 mutations. Here, we performed a comprehensive phenotypic characterization of a C8orf37 KO mouse line, generated using CRISPR/Cas9 technology. Both C8orf37 KO male and female mice exhibited progressive and simultaneous degeneration of rod and cone photoreceptors but no non-ocular phenotypes. The major ultrastructural feature of C8orf37 KO photoreceptors was massive disorganization of the outer segment (OS) membrane discs starting from the onset of disc morphogenesis during development. At the molecular level, the amounts of multiple OS-specific membrane proteins, including proteins involved in membrane disc organization, were reduced, although these proteins were targeted normally to the OS. Considering the distribution of C8ORF37 throughout the photoreceptor cell body, the normal structure of the KO photoreceptor connecting cilium, and the absence of defects in other ciliary organs of the KO mice, our findings do not support the previous notion that C8ORF37 was a ciliary protein. Because C8ORF37 is absent in the photoreceptor OS, C8ORF37 may participate in the secretory pathway of OS membrane proteins in the photoreceptor cell body and thus maintain the homeostasis of these proteins. This study established a valid animal model for future therapeutic studies of C8ORF37-associated retinal degeneration. This study also shed new light on the role of C8ORF37 in photoreceptors and on the pathogenic mechanism underlying retinal degeneration caused by C8ORF37 mutations.SIGNIFICANCE STATEMENT Inherited retinal degeneration is a group of incurable conditions with poorly understood underlying molecular mechanisms. We investigated C8ORF37, a causative gene for three retinal degenerative conditions: retinitis pigmentosa, cone-rod dystrophy, and Bardet-Biedl syndrome. C8ORF37 encodes a protein with no known functional domains and thus its biological function is unpredictable. We knocked out the C8ORF37 ortholog in mice, which resulted in a retinal phenotype similar to that observed in patients. We further demonstrated that C8ORF37 is required for photoreceptor outer segment disc formation and alignment, a process that is critical for photoreceptor function and survival. This study advances our understanding of the pathogenesis of retinal degeneration and establishes a valuable mouse model for future therapeutic development.

Dataset Information

Light regulates the ciliary protein transport and outer segment disc renewal of mammalian photoreceptors.

Publications

Light regulates the ciliary protein transport and outer segment disc renewal of mammalian photoreceptors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets