A lysosomal tetraspanin associated with retinal degeneration identified via a genome-wide screen

EMBO J. 2004 Feb 25;23(4):811-22. doi: 10.1038/sj.emboj.7600112. Epub 2004 Feb 12.

Abstract

The Drosophila visual system has provided a model to study phototransduction and retinal degeneration. To identify new candidate proteins that contribute to these processes, we conducted a genome-wide screen for genes expressed predominately in the eye, using DNA microarrays. This screen appeared to be comprehensive as it led to the identification of all 22 eye-enriched genes previously shown to function in phototransduction or implicated in retinal degeneration. In addition, we identified 93 eye-enriched genes whose roles have not been previously defined. One of the eye-enriched genes encoded a member of a large family of transmembrane proteins, referred to as tetraspanins. We created a null mutation in the eye-enriched tetraspanin, Sunglasses (Sun), which resulted in light-induced retinal degeneration. We found that the Sun protein was distributed primarily in lysosomes, and functioned in a long-known but poorly understood phenomenon of light-induced degradation of rhodopsin. We propose that lysosomal tetraspanins in mammalian cells may also function in the downregulation of rhodopsin and other G-protein-coupled receptors, in response to intense or prolonged agonist stimulation.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Lysosomes / genetics
  • Lysosomes / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microscopy, Electron, Transmission
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Retinal Degeneration / genetics
  • Rhodopsin / biosynthesis
  • Rhodopsin / genetics

Substances

  • Drosophila Proteins
  • Eye Proteins
  • Membrane Proteins
  • Tsp42Ej protein, Drosophila
  • Rhodopsin