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

PLoS Biol. 2012;10(12):e1001438. doi: 10.1371/journal.pbio.1001438. Epub 2012 Dec 4.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Animals
  • Cytoplasm / metabolism
  • Cytoplasm / radiation effects
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Drosophila melanogaster / radiation effects
  • Electroretinography
  • Female
  • Gene Knockdown Techniques
  • Genes, Insect / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Light
  • Male
  • Mutation / genetics
  • Photoreceptor Cells, Invertebrate / metabolism*
  • Photoreceptor Cells, Invertebrate / pathology
  • Photoreceptor Cells, Invertebrate / radiation effects
  • Photoreceptor Cells, Invertebrate / ultrastructure
  • Protein Binding / radiation effects
  • Protein Transport / radiation effects
  • Retinal Degeneration / pathology
  • Retinal Degeneration / physiopathology
  • Rhodopsin / metabolism*
  • rab GTP-Binding Proteins / metabolism*

Substances

  • Crag protein, Drosophila
  • Drosophila Proteins
  • Guanine Nucleotide Exchange Factors
  • ninaE protein, Drosophila
  • Rhodopsin
  • Rab11 protein, Drosophila
  • rab GTP-Binding Proteins