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

Hong Xu, Seung Jae Lee, Emiko Suzuki, Katherine D. Dugan, Alexander Stoddard, Hong Sheng Li, Lewis A. Chodosh, Craig Montell

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)811-822
Number of pages12
JournalThe EMBO journal
Volume23
Issue number4
DOIs
StatePublished - Feb 25 2004

Keywords

  • Drosophila
  • Microarray
  • Phototransduction
  • Retinal degeneration
  • Rhodopsin
  • Tetraspanin

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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