Single amino acid change in the fifth transmembrane segment of the TRP Ca2+ channel causes massive degeneration of photoreceptors.
The trp gene encodes subunits of a highly Ca(2+)-permeable class of light-activated channels of Drosophila photoreceptors. The recently characterized mutation in this gene, Trp(P365), is semidominant and causes massive degeneration of photoreceptors by making the TRP channel constitutively active. We show that a single amino acid change, Phe-550 to Ile, near the beginning of the fifth transmembrane domain of TRP channel subunits is necessary to induce, and sufficient to closely mimic, the original mutant phenotypes of Trp(P365). Hypotheses are presented as to why the amino acid residues at position 550 and its immediate vicinity might be important in influencing the regulation of the TRP channel and why the substitution of Phe for Ile at this position, in particular, could result in constitutive activity of the channel.
Hong
Young Seok
YS
Department of Biological Sciences, Purdue University, 1392 Lilly Hall, West Lafayette, IN 47907, USA.
Park
Soyeon
S
Geng
Chaoxian
C
Baek
Kwanghee
K
Bowman
John D
JD
Yoon
Jaeseung
J
Pak
William L
WL
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D015220:Calcium Channels / Q000737:chemistry* / Q000502:physiology; D004330:Drosophila; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010786:Photoreceptor Cells / Q000473:pathology*; D017354:Point Mutation; D012162:Retinal Degeneration / Q000209:etiology*; D013329:Structure-Activity Relationship; D050052:TRPC Cation Channels
D015220:Calcium Channels; D050052:TRPC Cation Channels