Article
- The EMBO Journal (2004) 23, 811 - 822
- doi:10.1038/sj.emboj.7600112
Published online: 12 February 2004
Subject Categories:
A lysosomal tetraspanin associated with retinal degeneration identified via a genome-wide screen
Hong Xu1, Seung-Jae Lee1, Emiko Suzuki2, Katherine D Dugan3, Alexander Stoddard3, Hong-Sheng Li1,a, Lewis A Chodosh3 and Craig Montell1
- Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Basic Medical Sciences, The University of Tokyo, Tokyo, Japan
- Department of Cancer Biology and Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Correspondence to:
Craig Montell, Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 N Wolfe St., 408 WBSB, Baltimore, MD 21205, USA. Tel.: +1 410 955 1199; Fax: +1 410 614 9573; E-mail: cmontell@jhmi.edu
aPresent address: Department of Neurobiology, Medical School, University of Massachusetts, Worcester, MA 01655, USA
Received 14 October 2003; Accepted 15 January 2004
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.
Keywords:
- Drosophila,
- microarray,
- phototransduction,
- retinal degeneration,
- rhodopsin,
- tetraspanin
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