title: Single amino acid change in the fifth transmembrane segment of the TRP Ca2+ channel causes massive degeneration of photoreceptors.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Purdue University, 1392 Lilly Hall, West Lafayette, IN 47907, USA.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Hong
authors.forename: Soyeon
authors.initials: S
authors.lastname: Park
authors.forename: Chaoxian
authors.initials: C
authors.lastname: Geng
authors.forename: Kwanghee
authors.initials: K
authors.lastname: Baek
authors.forename: John D
authors.initials: JD
authors.lastname: Bowman
authors.forename: Jaeseung
authors.initials: J
authors.lastname: Yoon
authors.forename: William L
authors.initials: WL
authors.lastname: Pak
mesh_terms: 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
chemical_list: D015220:Calcium Channels; D050052:TRPC Cation Channels