Rhodopsin and phototransduction: a model system for G protein‐linked receptors

Hargrave, Paul A.; McDowell, J. Hugh

doi:10.1096/fasebj.6.6.1544542

Cited by 304 publications

(172 citation statements)

References 2 publications

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“…Once properly localized in ROS, rhodopsin and other factors participate in a cascade of signaling interactions triggered by light (5). Maintaining polarized organization throughout the continuous ROS renewal, which results in the addition of up to 3 m 2 ͞min of membrane (6), is of paramount importance for the health of photoreceptor cells.…”

mentioning

confidence: 99%

Regulation of sorting and post-Golgi trafficking of rhodopsin by its C-terminal sequence QVS(A)PA

Deretic

Schmerl

Hargrave

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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Several mutations that cause severe forms of the human disease autosomal dominant retinitis pigmentosa cluster in the C-terminal region of rhodopsin. Recent studies have implicated the C-terminal domain of rhodopsin in its trafficking on specialized post-Golgi membranes to the rod outer segment of the photoreceptor cell. Here we used synthetic peptides as competitive inhibitors of rhodopsin trafficking in the frog retinal cell-free system to delineate the potential regulatory sequence within the C terminus of rhodopsin and model the effects of severe retinitis pigmentosa alleles on rhodopsin sorting. The rhodopsin C-terminal sequence QVS(A)PA is highly conserved among different species. Peptides that correspond to the C terminus of bovine (amino acids 324-348) and frog (amino acids 330-354) rhodopsin inhibited post-Golgi trafficking by 50% and 60%, respectively, and arrested newly synthesized rhodopsin in the trans-Golgi network. Peptides corresponding to the cytoplasmic loops of rhodopsin and other control peptides had no effect. When three naturally occurring mutations: Q344ter (lacking the last five amino acids QVAPA), V345M, and P347S were introduced into the frog C-terminal peptide, the inhibitory activity of the peptides was no longer detectable. These observations suggest that the amino acids QVS(A)PA comprise a signal that is recognized by specific factors in the trans-Golgi network. A lack of recognition of this sequence, because of mutations in the last five amino acids causing autosomal dominant retinitis pigmentosa, most likely results in abnormal post-Golgi membrane formation and in an aberrant subcellular localization of rhodopsin.Rhodopsin and the associated proteins and lipids are delivered by polarized sorting on post-Golgi membranes to the rod outer segment (ROS), a specialized domain of retinal photoreceptor cells (1-4). Once properly localized in ROS, rhodopsin and other factors participate in a cascade of signaling interactions triggered by light (5). Maintaining polarized organization throughout the continuous ROS renewal, which results in the addition of up to 3 m 2 ͞min of membrane (6

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mentioning

confidence: 99%

Regulation of sorting and post-Golgi trafficking of rhodopsin by its C-terminal sequence QVS(A)PA

Deretic

Schmerl

Hargrave

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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135

133

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“…Thus, the differences in photoresponse patterns between rods and cones should originate from the different properties of these proteins. Since the signal transduction proteins present in cones have amino acid sequences different from those of their counterparts in rods (1)(2)(3), identification of the amino acid residue(s) responsible for the molecular properties is important for furthering our understanding of the molecular mechanisms that underlie physiological differences between rods and cones.…”

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confidence: 99%

“…Among the signal transduction proteins, visual pigment receives a light signal from the environment using a light absorbing chromophore, 11-cis-retinal (3,4) and transfers the signal to the retinal G protein transducin by binding to it and catalyzing the GDP-GTP exchange reaction (1)(2)(3). In most vertebrates, different types of visual pigments are present in rod and cone photoreceptor cells.…”

mentioning

confidence: 99%

Single amino acid residue as a functional determinant of rod and cone visual pigments

Imai

Kojima

Oura

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

137

141

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The visual transduction processes in rod and cone photoreceptor cells begin with photon absorption by the different types of visual pigments. Cone visual pigments exhibit faster regeneration from 11-cis-retinal and opsin and faster decay of physiologically active intermediate (meta II) than does the rod visual pigment, rhodopsin, as expected, due to the functional difference between rod and cone photoreceptor cells. To identify the amino acid residue(s) responsible for the difference in molecular properties between rod and cone visual pigments, we selected three amino acid positions (64, 122, and 150), where cone visual pigments have amino acid residues electrically different from those of rhodopsin, and prepared mutants of rhodopsin and chicken greensensitive cone visual pigment. The results showed that the replacement of Glu-122 of rhodopsin by the residue containing green-or red-sensitive cone pigment converted rhodopsin's rates of regeneration and meta II decay into those of the respective cone pigments, whereas the introduction of Glu-122 into green-sensitive cone visual pigment changed the rates of these processes into rates similar to those of rhodopsin. Furthermore, exchange of the residue at position 122 between rhodopsin and chicken green-sensitive cone pigment interchanges their efficiencies in activating retinal G protein transducin. Thus, the amino acid residue at position 122 is a functional determinant of rod and cone visual pigments.

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“…Visual pigments respond to light by going through a series of photo-intermediates leading to a metastable state (metarhodopsin II) that stimulates transducin (47). The metarhodopsin II state decays to the apoprotein plus all-trans-retinal, and the time course of the decay plays an important role in phototransduction.…”

Section: Fig 3 Purification Of P-opsinmentioning

confidence: 99%

Light-dependent Activation of Rod Transducin by Pineal Opsin

Max¹,

Surya²,

Takahashi³

et al. 1998

Journal of Biological Chemistry

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The pineal gland expresses a unique member of the opsin family (P-opsin; Max, M., McKinnon, P. J., Seidenman, K. J., Barrett, R. K., Applebury, M. L., Takahashi, J. S., and Margolskee, R. F. (1995) Science 267, 1502-1506) that may play a role in circadian entrainment and photo-regulation of melatonin synthesis. To study the function of this protein, an epitope-tagged P-opsin was stably expressed in an embryonic chicken pineal cell line. When incubated with 11-cis-retinal, a light-sensitive pigment was formed with a max at 462 ؎ 2 nm. P-opsin bleached slowly in the dark (t 1/2 ‫؍‬ 2 h) in the presence of 50 mM hydroxylamine. Purified P-opsin in dodecyl maltoside activated rod transducin in a light-dependent manner, catalyzing the exchange of more than 300 mol of GTP␥S (guanosine 5-O-(3-thiotriphosphate))/mol of P-opsin. The initial rate for activation (75 mol of GTP␥S bound/mol of P-opsin/min at 7 M) increased with increasing concentrations of transducin. The addition of egg phosphatidylcholine to P-opsin had little effect on the activation kinetics; however, the intrinsic rate of decay in the absence of transducin was accelerated. These results demonstrate that P-opsin is an efficient catalyst for activation of rod transducin and suggest that the pineal gland may contain a rodlike phototransduction cascade.

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Rhodopsin and phototransduction: a model system for G protein‐linked receptors

Cited by 304 publications

References 2 publications

Regulation of sorting and post-Golgi trafficking of rhodopsin by its C-terminal sequence QVS(A)PA

Regulation of sorting and post-Golgi trafficking of rhodopsin by its C-terminal sequence QVS(A)PA

Single amino acid residue as a functional determinant of rod and cone visual pigments

Light-dependent Activation of Rod Transducin by Pineal Opsin

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