PMID- 10632594
OWN - NLM
STAT- MEDLINE
DCOM- 20000209
LR  - 20191023
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 20
IP  - 2
DP  - 2000 Jan 15
TI  - Novel mechanism of massive photoreceptor degeneration caused by mutations in the 
      trp gene of Drosophila.
PG  - 649-59
AB  - The Drosophila trp gene encodes a light-activated Ca(2+) 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, 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.
FAU - Yoon, J
AU  - Yoon J
AD  - Institute of Genetic Engineering and Natural Sciences, Department of Genetic 
      Engineering, KyungHee University, Yongin City, Kyungki-Do, 449-701 Korea.
FAU - Ben-Ami, H C
AU  - Ben-Ami HC
FAU - Hong, Y S
AU  - Hong YS
FAU - Park, S
AU  - Park S
FAU - Strong, L L
AU  - Strong LL
FAU - Bowman, J
AU  - Bowman J
FAU - Geng, C
AU  - Geng C
FAU - Baek, K
AU  - Baek K
FAU - Minke, B
AU  - Minke B
FAU - Pak, W L
AU  - Pak WL
LA  - eng
GR  - EY00033/EY/NEI NIH HHS/United States
GR  - EY03529/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Calcium Channels)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (transient receptor potential cation channel, subfamily C, member 1)
SB  - IM
MH  - Amino Acid Sequence
MH  - *Amino Acid Substitution
MH  - Animals
MH  - Calcium Channels/chemistry/*genetics/metabolism
MH  - *Chromosome Mapping
MH  - Drosophila melanogaster/*genetics/physiology
MH  - Electroretinography
MH  - Genes, Insect
MH  - Humans
MH  - Microscopy, Confocal
MH  - Molecular Sequence Data
MH  - Nerve Degeneration/genetics
MH  - Phenotype
MH  - Photoreceptor Cells, Invertebrate/*cytology/*physiology
MH  - *Point Mutation
MH  - Retina/ultrastructure
MH  - TRPC Cation Channels
PMC - PMC6772429
EDAT- 2000/01/13 00:00
MHDA- 2000/01/13 00:01
CRDT- 2000/01/13 00:00
PHST- 2000/01/13 00:00 [pubmed]
PHST- 2000/01/13 00:01 [medline]
PHST- 2000/01/13 00:00 [entrez]
AID - 3808 [pii]
AID - 10.1523/JNEUROSCI.20-02-00649.2000 [doi]
PST - ppublish
SO  - J Neurosci. 2000 Jan 15;20(2):649-59. doi: 10.1523/JNEUROSCI.20-02-00649.2000.