Arrestin1 mediates light-dependent rhodopsin endocytosis and cell survival

Curr Biol. 2005 Oct 11;15(19):1722-33. doi: 10.1016/j.cub.2005.08.064.


Background: Arrestins are pivotal, multifunctional organizers of cell responses to GPCR stimulation, including cell survival and cell death. In Drosophila norpA and rdgC mutants, endocytosis of abnormally stable complexes of rhodopsin (Rh1) and fly photoreceptor Arrestin2 (Arr2) triggers cell death, implicating Rh1/Arr2-bearing endosomes in pro-cell death signaling, potentially via arrestin-mediated GPCR activation of effector kinase pathways. In order to further investigate arrestin function in photoreceptor physiology and survival, we studied Arr2's partner photoreceptor arrestin, Arr1, in developing and adult Drosophila compound eyes.

Results: We report that Arr1, but not Arr2, is essential for normal, light-induced rhodopsin endocytosis. Also distinct from Arr2, Arr1 is essential for light-independent photoreceptor survival. Photoreceptor cell death caused by loss of Arr1 is strongly suppressed by coordinate loss of Arr2. We further find that Rh1 C-terminal phosphorylation is essential for light-induced endocytosis and also for translocation of Arr1, but not Arr2, from dark-adapted photoreceptor cytoplasm to photosensory membrane rhabdomeres. In contrast to a previous report, we do not find a requirement for photoreceptor myosin kinase NINAC in Arr1 or Arr2 translocation.

Conclusions: The two Drosophila photoreceptor arrestins mediate distinct and essential cell pathways downstream of rhodopsin activation. We propose that Arr1 mediates an endocytotic cell-survival activity, scavenging phosphorylated rhodopsin and thereby countering toxic Arr2/Rh1 accumulation; elimination of toxic Arr2/Rh1 in double mutants could thus rescue arr1 mutant photoreceptor degeneration.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arrestins / metabolism*
  • Arrestins / physiology
  • Blotting, Western
  • Cell Survival / physiology
  • Drosophila / physiology*
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology
  • Endocytosis / physiology*
  • Immunohistochemistry
  • Microscopy, Electron
  • Phosphorylation
  • Photoreceptor Cells, Invertebrate / physiology*
  • Photoreceptor Cells, Invertebrate / ultrastructure
  • Protein Binding
  • Rhodopsin / metabolism*


  • Arr1 protein, Drosophila
  • Arr2 protein, Drosophila
  • Arrestins
  • Drosophila Proteins
  • Rhodopsin