The Molecular Biology of the Rod Photoreceptor cGMP Phosphodiesterase α- and β-Subunits
Defects in proteins that function in photoreceptor signal transduction are prime suspects as causes of some hereditary retinal degenerations. Recently, a defect in the gene encoding the β-subunit of rod cGMP phosphodiesterase has been implicated as causative of the rd phenotype in mouse (Bowes et al. 1989, 1990), in which rod outer segments do not form properly prior to the onset of photoreceptor cell degeneration. We have characterized cDNA clones encoding the rod cGMP phosphodiesterase α -subunit of bovine, human, and mouse. We have further used bovine a-subunit sequences under low stringency conditions to identify clones encoding the mouse cGMP phosphodiesterase β-subunit. The similarity of the α-subunit sequences among species is greater than 90%, the similarity of mouse a and P-subunit cDNAs is approximately 73%. The open reading frames predict α-subunits of 100 kd, and a β-subunit of 99 kd. The domains most variable between the α-subunit are near the C-terminus; between the mouse α and β-subunit, at the N- and C-termini. A 230 residue segment thought to contain at least part of the active site is present in the C-terminal half of both the α and β-subunits, suggesting that each subunit may exhibit enzyme activity.
KeywordsMouse Retina Caax Motif cGMP Phosphodiesterase Hereditary Retinal Degeneration Putative Catalytic Domain
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