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

Shiuan Wang, Kai Li Tan, Melina A Agosto, Bo Xiong, Shinya Yamamoto, Hector Sandoval, Manish Jaiswal, Vafa Bayat, Ke Zhang, Wu-Lin Charng, Gabriela David, Lita Duraine, Kartik Venkatachalam, Theodore G Wensel, Hugo J Bellen

Research output: Contribution to journalArticle

43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)e1001847
JournalPLoS biology
Volume12
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • Animals
  • Drosophila Proteins
  • Drosophila melanogaster
  • Endocytosis
  • Light
  • Lysosomes
  • Mutation
  • Photoreceptor Cells, Invertebrate
  • Protein Transport
  • Retinal Degeneration
  • Rhodopsin
  • Vesicular Transport Proteins
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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