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Previous Article | Next Article
The Journal of Neuroscience, January 15, 2000, 20(2):649-659
Novel Mechanism of Massive Photoreceptor Degeneration Caused by Mutations in the trp Gene of Drosophila
Jaeseung Yoon2, Hagit Cohen Ben-Ami3, Young Seok Hong1, Soyeon Park2, Lydia L. R. Strong1, John Bowman1, Chaoxian Geng1, Kwanghee Baek2, Baruch Minke3, and William L. Pak1 1 Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, 2 Institute of Genetic Engineering and Natural Sciences, Department of Genetic Engineering, KyungHee University, Yongin City, Kyungki-Do, 449-701 Korea, and 3 Department of Physiology and the Kuhne Minerva Center for Studies of Visual Transduction, The Hebrew University, Hadassah Medical School, Jerusalem, Israel
The Drosophila trp gene encodes a light-activated Ca2+ channel subunit, which is a prototypical member of a novel class of channel proteins. Previously identified trp mutants are all recessive, loss-of-function mutants characterized by a transient receptor potential and the total or near-total loss of functional TRP protein. Although retinal degeneration does occur in these mutants, it is relatively mild and slow in onset. We report herein a new mutant, TrpP365, that does not display the transient receptor potential phenotype and is characterized by a substantial level of the TRP protein and rapid, semi-dominant degeneration of photoreceptors. We show that, in spite of its unusual phenotypes, TrpP365 is a trp allele because a TrpP365 transgene induces the mutant phenotype in a wild-type background, and a wild-type trp transgene in a TrpP365 background suppresses the mutant phenotype. Moreover, amino acid alterations that could cause the TrpP365 phenotype are found in the transmembrane segment region of the mutant channel protein. Whole-cell recordings clarified the mechanism underlying the retinal degeneration by showing that the TRP channels of TrpP365 are constitutively active. Although several genes, when mutated, have been shown to cause retinal degeneration in Drosophila, the underlying mechanism has not been identified for any of them. The present studies provide evidence for a specific mechanism for massive degeneration of photoreceptors in Drosophila. Insofar as some human homologs of TRP are highly expressed in the brain, a similar mechanism could be a major contributor to degenerative disorders of the brain.
Key words: TRP Ca2+ channel; photoreceptor degeneration; novel mechanism of neuronal cell death; semi-dominant trp mutant; constitutive channel activity; Drosophila
Copyright © 2000 Society for Neuroscience 0270-6474/00/202649-11$05.00/0
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