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

• Published in: The EMBO journal 2004-02, Vol.23 (4), p.811-822
• Main Authors: Xu, Hong, Lee, Seung-Jae, Suzuki, Emiko, Dugan, Katherine D, Stoddard, Alexander, Li, Hong-Sheng, Chodosh, Lewis A, Montell, Craig
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Deoxyribonucleic acid; DNA; DNA arrays; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; EMBO27; EMBO37; Eye; Eye Proteins - genetics; Eye Proteins - metabolism; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; Lysosomes - genetics; Lysosomes - metabolism; Mammals; Membrane Proteins - genetics; Membrane Proteins - metabolism; microarray; Microscopy, Electron, Transmission; Molecular Sequence Data; Mutation; Oligonucleotide Array Sequence Analysis; phototransduction; Proteins; retinal degeneration; Retinal Degeneration - genetics; rhodopsin; Rhodopsin - biosynthesis; Rhodopsin - genetics; Sun protein; Sunglasses protein; tetraspanin
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7600112

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.