title: The role of arrestin and retinoids in the regeneration pathway of rhodopsin.
abstract: Phototransduction results from a cascade of reactions that culminate in a neuronal signal. Photoisomerization of rhodopsin's chromophore, 11-cis-retinal to all-trans-retinal, leads to the formation of the activated photoproduct metarhodopsin II (Meta II). Subsequently, Meta II initiates the excitation events by activating many copies of the rod cell-specific G-proteins (Gt or transducin). To terminate the signal, the long-lived Meta II must be quenched. Deactivation of Meta II involves phosphorylation by rhodopsin kinase followed by the binding of arrestin. In order to recycle rhodopsin for phototransduction, arrestin must dissociate, and the chromophore must be replaced. In this study, we show that the reduction of the photolyzed chromophore all-trans-retinal to all-trans-retinol is essential for recycling photoactivated rhodopsin. Once this reduction has occurred, the arrestin blockade of the receptor is removed, the chromophore site becomes accessible for regeneration, and the phosphates can be hydrolyzed. If the reduction does not occur, we demonstrate that free all-trans-retinal can react with the apoprotein to form pseudo-photoproducts that are spectrally identical to the photoinduced metarhodopsin species (Meta I/II/III). The Meta II-like product, M380, interacts tightly with arrestin and kinase, however, it does not measurably interact with Gt. The persistent blockade by arrestin and the low affinity for Gt together prevent activation of the visual cascade. Therefore, any insufficiency in the reduction of all-trans-retinal to all-trans-retinol may lead to the accumulation of M380-arrestin in situ, which may effect adaptational processes.
authors.affiliation: Institut für Biophysik und Strahlenbiologie, Universität Freiburg, Federal Republic of Germany.
authors.forename: K P
authors.initials: KP
authors.lastname: Hofmann
authors.forename: A
authors.initials: A
authors.lastname: Pulvermüller
authors.forename: J
authors.initials: J
authors.lastname: Buczyłko
authors.forename: P
authors.initials: P
authors.lastname: Van Hooser
authors.forename: K
authors.initials: K
authors.lastname: Palczewski
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000378:metabolism*; D019393:Arrestin; D002417:Cattle; D005136:Eye Proteins / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008027:Light; D008954:Models, Biological; D010766:Phosphorylation; D010786:Photoreceptor Cells / Q000378:metabolism; D012172:Retinaldehyde / Q000494:pharmacology; D012176:Retinoids / Q000378:metabolism*; D012243:Rhodopsin / Q000031:analogs & derivatives / Q000378:metabolism*; D017299:Rod Opsins
chemical_list: D000941:Antigens; D019393:Arrestin; D005136:Eye Proteins; D012176:Retinoids; D017299:Rod Opsins; C013110:metarhodopsins; D000255:Adenosine Triphosphate; D012243:Rhodopsin; D012172:Retinaldehyde