TY - JOUR
T1 - Novel mechanism of massive photoreceptor degeneration caused by mutations in the trp gene of Drosophila
AU - Yoon, Jaeseung
AU - Ben-Ami, Hagit Cohen
AU - Hong, Young Seok
AU - Park, Soyeon
AU - Strong, Lydia L.R.
AU - Bowman, John
AU - Geng, Chaoxian
AU - Baek, Kwanghee
AU - Minke, Baruch
AU - Pak, William L.
PY - 2000/1/15
Y1 - 2000/1/15
N2 - 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 dr 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, Trp(P365), 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, Trp(P365) is a trp allele because a Trp(P365) transgene induces the mutant phenotype in a wild-type background, and a wild- type trp transgene in a Trp(P365) background suppresses the mutant phenotype. Moreover, amino acid alterations that could cause the Trp(P365) 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 Trp(P365) 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.
AB - 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 dr 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, Trp(P365), 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, Trp(P365) is a trp allele because a Trp(P365) transgene induces the mutant phenotype in a wild-type background, and a wild- type trp transgene in a Trp(P365) background suppresses the mutant phenotype. Moreover, amino acid alterations that could cause the Trp(P365) 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 Trp(P365) 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.
KW - Constitutive channel activity
KW - Drosophila
KW - Novel mechanism of neuronal cell death
KW - Photoreceptor degeneration
KW - Semi-dominant trp mutant
KW - TRP Ca channel
UR - http://www.scopus.com/inward/record.url?scp=17944393022&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.20-02-00649.2000
DO - 10.1523/jneurosci.20-02-00649.2000
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C2 - 10632594
AN - SCOPUS:17944393022
SN - 0270-6474
VL - 20
SP - 649
EP - 659
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 2
ER -