The retromer complex is required for rhodopsin recycling and its loss leads to photoreceptor degeneration.
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.
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Shiuan
S
Wang
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Kai Li
KL
Tan
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Melina A
MA
Agosto
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Bo
B
Xiong
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.
Shinya
S
Yamamoto
Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
Hector
H
Sandoval
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.
Manish
M
Jaiswal
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Vafa
V
Bayat
Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas, United States of America.
Ke
K
Zhang
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Wu-Lin
WL
Charng
Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Gabriela
G
David
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.
Lita
L
Duraine
Department of Integrative Biology and Pharmacology, University of Texas School of Medicine, Houston, Texas, United States of America.
Kartik
K
Venkatachalam
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Theodore G
TG
Wensel
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.
Hugo J
HJ
Bellen
D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D008027:Light; D008247:Lysosomes / Q000378:metabolism; D009154:Mutation; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport; D012162:Retinal Degeneration / Q000503:physiopathology; D012243:Rhodopsin / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism
D029721:Drosophila Proteins; D033921:Vesicular Transport Proteins; C528433:Vps26 protein, Drosophila; C527271:Vps35 protein, Drosophila; D012243:Rhodopsin