title: In vivo differential prenylation of retinal cyclic GMP phosphodiesterase catalytic subunits.
abstract: A number of phototransducing proteins in vertebrate photoreceptors contain a carboxyl terminal -CXXX motif (where C = cysteine and X = any amino acid), known to be a signal sequence for their post-translational prenylation and carboxyl methylation. To study the roles of these modifications in the visual excitation process, we have utilized an intravitreal injection method to radiolabel the prenylated proteins of rat retinas in vivo. We showed that two of the major prenylated polypeptides in the rod outer segments are the PDE alpha and PDE beta subunits of cyclic GMP phosphodiesterase PDE alpha and PDE beta subunits of cyclic GMP phosphodiesterase (PDE). By chromatographic analyses of the amino acid constituents generated by exhaustive proteolysis of PDE alpha and PDE beta, we further demonstrated that they are differentially prenylated by farnesylation and geranylgeranylation, respectively. While a number of proteins ending with the -CXXX sequence have already been reported to possess either a farnesyl or a geranylgeranyl group, PDE is the first enzyme shown to be modified by both types of prenyl groups. The prenyl modification of PDE most likely plays a major role in membrane attachment and in correctly positioning the PDE molecule for phototransduction.
authors.affiliation: Jules Stein Eye Institute, University of California, Los Angeles 90024.
authors.forename: J S
authors.initials: JS
authors.lastname: Anant
authors.forename: O C
authors.initials: OC
authors.lastname: Ong
authors.forename: H Y
authors.initials: HY
authors.lastname: Xie
authors.forename: S
authors.initials: S
authors.lastname: Clarke
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Brien
authors.forename: B K
authors.initials: BK
authors.lastname: Fung
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational; D051381:Rats; D011919:Rats, Inbred Strains; D012374:Rod Cell Outer Segment / Q000201:enzymology*
chemical_list: D015106:3',5'-Cyclic-GMP Phosphodiesterases