The Retromer Complex Is Required for Rhodopsin Recycling and Its Loss Leads to Photoreceptor Degeneration
Year: 2014
Type: article
Abstract: Rhodopsin mistrafficking can cause photoreceptor (PR) degeneration. Upon light exposure, activated rhodopsin 1 (Rh1) in Drosophila PRs is internalized via endocytosis and degraded in lysosomes. Whether internalized Rh1 can be recycled is unknown. Here, we show that the retromer complex is expressed in PRs where it is required for recycling endocytosed Rh1 upon light stimulation. In the absence of subunits of the retromer, Rh1 is processed in the endolysosomal pathway, leading to a dramatic increase in late endosomes, lysosomes, and light-dependent PR degeneration. Reducing Rh1 endocytosis or Rh1 levels in retromer mutants alleviates PR degeneration. In addition, increasing retromer abundance suppresses degenerative phenotypes of mutations that affect the endolysosomal system. Finally, expressing human Vps26 suppresses PR degeneration in Vps26 mutant PRs. We propose that the retromer plays a conserved role in recycling rhodopsins to maintain PR function and integrity.
Source: PLoS Biology
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,500
Funders: Howard Hughes Medical Institute, Welch Foundation, Knights Templar Eye Foundation, Ögonfonden, National Science Council, National Institutes of Health, Intellectual and Developmental Disabilities Research Center, National Eye Institute, National Institute of General Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Trasnducin Interactions with Photoreceptor Membranes, Research Education and Career Horizons Program, Mapping and rescuing EMS-induced lethal mutations on the Drosophila X Chromosome, G448816448, G5342805898, Baylor Intellectual and Developmental Disabilities Research Center, Developmental Biology Training Program, A Comprehensive Resource for Manipulating the Drosophila Genome
OpenAlex ID: W1967281511