Crag is a GEF for Rab11 required for rhodopsin trafficking and maintenance of adult photoreceptor cells

Bo Xiong, Vafa Bayat, Manish Jaiswal, Ke Zhang, Hector Sandoval, Wu-Lin Charng, Tongchao Li, Gabriela David, Lita Duraine, Yong-Qi Lin, G Gregory Neely, Shinya Yamamoto, Hugo J Bellen

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Rhodopsins (Rhs) are light sensors, and Rh1 is the major Rh in the Drosophila photoreceptor rhabdomere membrane. Upon photoactivation, a fraction of Rh1 is internalized and degraded, but it remains unclear how the rhabdomeric Rh1 pool is replenished and what molecular players are involved. Here, we show that Crag, a DENN protein, is a guanine nucleotide exchange factor for Rab11 that is required for the homeostasis of Rh1 upon light exposure. The absence of Crag causes a light-induced accumulation of cytoplasmic Rh1, and loss of Crag or Rab11 leads to a similar photoreceptor degeneration in adult flies. Furthermore, the defects associated with loss of Crag can be partially rescued with a constitutive active form of Rab11. We propose that upon light stimulation, Crag is required for trafficking of Rh from the trans-Golgi network to rhabdomere membranes via a Rab11-dependent vesicular transport.

Original languageEnglish (US)
Pages (from-to)e1001438
JournalPLoS biology
Volume10
Issue number12
DOIs
StatePublished - 2012

Keywords

  • Aging
  • Animals
  • Cytoplasm
  • Drosophila Proteins
  • Drosophila melanogaster
  • Electroretinography
  • Female
  • Gene Knockdown Techniques
  • Genes, Insect
  • Guanine Nucleotide Exchange Factors
  • Light
  • Male
  • Mutation
  • Photoreceptor Cells, Invertebrate
  • Protein Binding
  • Protein Transport
  • Retinal Degeneration
  • Rhodopsin
  • rab GTP-Binding Proteins
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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