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PLoS Biol. 2014 Apr 29;12(4):e1001847. doi: 10.1371/journal.pbio.1001847. eCollection 2014 Apr.

The retromer complex is required for rhodopsin recycling and its loss leads to photoreceptor degeneration.

Author information

1
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
2
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
3
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas, United States of America; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, United States of America.
4
Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
5
Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas, United States of America; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, United States of America.
6
Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
7
Department of Integrative Biology and Pharmacology, University of Texas School of Medicine, Houston, Texas, United States of America.
8
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas, United States of America; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, United States of America; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, United States of America; Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas, United States of America; Department of Neuroscience, Baylor College of Medicine, Houston, Texas, United States of America.

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.

PMID:
24781186
PMCID:
PMC4004542
DOI:
10.1371/journal.pbio.1001847
[Indexed for MEDLINE]
Free PMC Article

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