Sci. STKE, 7 November 2000
Apoptosis Murdered by Light
Light activates rhodopsin and a G protein-mediated signal transduction cascade. The rapid inactivation and resetting of the pathway by phosphorylation and arrestin interactions are essential for sensitivity to low light levels. Two groups (Alloway, Howard, and Dolph and Kiselev et al.) have determined that persistence of the arrestin-rhodopsin complex can cause light-induced retinal degeneration in Drosophila mutants defective in light-stimulated signal transduction. Apoptotic cell death caused by mutations that block light-induced signaling [rdgC (rhodopsin-specific Ca2+-dependent phosphatase), norpA (phospholipase C mutant defective in arrestin phosphorylation), and rdgB (phosphotidylinositol transfer protein)] could be rescued by mutants in arrestin that do not interact effectively with rhodospin or by decreasing rhodopsin levels. Alloway, Howard, and Dolph show that the retinal degeneration associated with norpA mutant flies was inhibited by expression of the caspase inhibitor p35 from baculovirus. Kiselev et al. provide evidence that formation of the arrestin-rhodopsin complexes leads to endocytosis of the complexes by a clathrin-mediated mechanism and that this internalization is also important for triggering apoptosis. How and why the internalized arrestin-rhodopsin complex causes cell death remains unclear.
Alloway, P.G., Howard, L., and Dolph, P.J. (2000) The formation of stable rhodopsin-arrestin complexes induces apoptosis and photoreceptor degeneration. Neuron 28: 129-128. [Online Journal]
Kiselev, A., Socolich, M., Vinós, J., Hardy, R.W., Zuker, C.S., and Ranganathan, R. (2000) A molecular pathway for light-dependent photoreceptor apoptosis in Drosophila. Neuron 28: 139-152. [Online Journal]
Citation: Murdered by Light. Sci. STKE 2000, tw4 (2000).
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