Beyond Counting Photons: Trials and Trends in Vertebrate Visual Transduction

Burns, Marie E.; Arshavsky, Vadim Y.

doi:10.1016/j.neuron.2005.10.014

Cited by 225 publications

(239 citation statements)

References 200 publications

(207 reference statements)

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“…The maximum rate in the native membrane still is about one order of magnitude higher than in solution (27,28). This finding may be explained by the reduction in translational degrees of freedom in a two-dimensional membrane, which facilitates successful coupling.…”

Section: Discussionmentioning

confidence: 92%

Monomeric G protein-coupled receptor rhodopsin in solution activates its G protein transducin at the diffusion limit

Ernst

Gramse

Kolbe

et al. 2007

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

200

163

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G protein-coupled receptors mediate biological signals by stimulating nucleotide exchange in heterotrimeric G proteins (G␣␤␥).Receptor dimers have been proposed as the functional unit responsible for catalytic interaction with G␣␤␥. To investigate whether a G protein-coupled receptor monomer can activate G␣␤␥, we used the retinal photoreceptor rhodopsin and its cognate G protein transducin (G t) to determine the stoichiometry of rhodopsin/Gt binding and the rate of catalyzed nucleotide exchange in G t. Purified rhodopsin was prepared in dodecyl maltoside detergent solution. Rhodopsin was monomeric as concluded from fluorescence resonance energy transfer, copurification studies with fluorescent labeled and unlabeled rhodopsin, size exclusion chromatography, and multiangle laser light scattering. A 1:1 complex between light-activated rhodopsin and G t was found in the elution profiles, and one molecule of GDP was released upon complex formation. Analysis of the speed of catalytic rhodopsin/G t interaction yielded a maximum of Ϸ50 Gt molecules per second and molecule of activated rhodopsin. The bimolecular rate constant is close to the diffusion limit in the diluted system. The results show that the interaction of Gt with an activated rhodopsin monomer is sufficient for fully functional Gt activation. Although the activation rate in solution is at the physically possible limit, the rate in the native membrane is still 10-fold higher. This is likely attributable to the precise orientation of the G protein to the membrane surface, which enables a fast docking process preceding the actual activation step. Whether docking in membranes involves the formation of rhodopsin dimers or oligomers remains to be elucidated. enzyme catalysis ͉ nucleotide exchange ͉ light scattering

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Section: Discussionmentioning

confidence: 92%

Monomeric G protein-coupled receptor rhodopsin in solution activates its G protein transducin at the diffusion limit

Ernst

Gramse

Kolbe

et al. 2007

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

200

163

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“…This dampening or adaptation is thought to be a protective consequence of prolonged stimulation, because indeed, adaptation protects mammalian photoreceptors from stimulationinduced degeneration (1,2). The cellular, molecular, and temporal controls that allow sensory neurons to switch from being responsive to refractory to a given stimulus are examined herein.…”

mentioning

confidence: 99%

Nuclear entry of a cGMP-dependent kinase converts transient into long-lasting olfactory adaptation

Lee

O'Halloran

Eastham-Anderson

et al. 2010

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

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To navigate a complex and changing environment, an animal's sensory neurons must continually adapt to persistent cues while remaining responsive to novel stimuli. Long-term exposure to an inherently attractive odor causes Caenorhabditis elegans to ignore that odor, a process termed odor adaptation. Odor adaptation is likely to begin within the sensory neuron, because it requires factors that act within these cells at the time of odor exposure. The process by which an olfactory sensory neuron makes a decisive shift over time from a receptive state to a lasting unresponsive one remains obscure. In C. elegans, adaptation to odors sensed by the AWC pair of olfactory neurons requires the cGMP-dependent protein kinase EGL-4. Using a fully functional, GFP-tagged EGL-4, we show here that prolonged odor exposure sends EGL-4 into the nucleus of the stimulated AWC neuron. This odor-induced nuclear translocation correlates temporally with the stable dampening of chemotaxis that is indicative of long-term adaptation. Long-term adaptation requires cGMP binding residues as well as an active EGL-4 kinase. We show here that EGL-4 nuclear accumulation is both necessary and sufficient to induce longlasting odor adaptation. After it is in the AWC nucleus, EGL-4 decreases the animal's responsiveness to AWC-sensed odors by acting downstream of the primary sensory transduction. Thus, the EGL-4 protein kinase acts as a sensor that integrates odor signaling over time, and its nuclear translocation is an instructive switch that allows the animal to ignore persistent odors.neuron | plasticity | signaling | memory | integration S ensory neurons, the entry point for information about an animal's external environment, must both respond to relevant stimuli and dampen their response as a consequence of prolonged stimulation. This dampening or adaptation is thought to be a protective consequence of prolonged stimulation, because indeed, adaptation protects mammalian photoreceptors from stimulationinduced degeneration (1, 2). The cellular, molecular, and temporal controls that allow sensory neurons to switch from being responsive to refractory to a given stimulus are examined herein. The Caenorhabditis elegans AWC sensory neuronal pair can sense (3) and adapt (4) to inherently attractive odors, and although both sensory and interneurons within the olfactory circuit adapt to persistent stimulation (5, 6), this focus will be on the events that instruct long-lasting adaptation within the sensory neuron.The AWC neurons (3, 7) are postulated to express at least 20 different odor-responsive G protein-coupled receptors (8, 9), use cGMP as a second messenger (10-13), and hyperpolarize in response to odor (14). Odor adaptation begins within 10 min of odor exposure, and there is a mild decrease in the animal's attraction to the odor accompanied by an increase in phosphorylated MAP kinase in AWC (5, 15) that requires the G protein gamma, GPC-1 (16). After 30 min of exposure, attraction decreases further as the animal enters a phase of short-term adaptation...

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“…2 The abbreviations used are: PDE, cyclic nucleotide phosphodiesterase; P␥, ␥-subunit of PDE6; G␣ t , transducin ␣-subunit; FRAP, fluorescence recovery after photobleaching; ROS, rod outer segment(s); RIS, rod inner segment(s).…”

mentioning

confidence: 99%

“…Eleven families of PDEs have been identified in mammals on the grounds of sequence homology, substrate selectivity, and regulation (1). Photoreceptor-specific PDEs in rods and cones comprise the sixth PDE family (PDE6) and serve as the effector enzymes in the vertebrate phototransduction cascade (1)(2)(3)(4)(5). Rod PDE6 is composed of homologous catalytic ␣-subunit (PDE6A) and ␤-subunit (PDE6B) and two copies of a small inhibitory ␥-subunit (P␥) (3).…”

mentioning

confidence: 99%

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Characterization of Human Cone Phosphodiesterase-6 Ectopically Expressed in Xenopus laevis Rods

Muradov

Boyd

Haeri

et al. 2009

Journal of Biological Chemistry

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PDE6 (phosphodiesterase-6) is the effector molecule in the vertebrate phototransduction cascade. Progress in understanding the structure and function of PDE6 has been hindered by lack of an expression system of the enzyme. Here we report ectopic expression and analysis of compartmentalization and membrane dynamics of the enhanced green fluorescent protein (EGFP) fusion protein of human cone PDE6C in rods of transgenic Xenopus laevis. EGFP-PDE6C is correctly targeted to the rod outer segments in transgenic Xenopus, where it displayed a characteristic striated pattern of EGFP fluorescence. Immunofluorescence labeling indicated significant and light-independent co-localization of EGFP-PDE6C with the disc rim marker peripherin-2 and endogenous frog PDE6. The diffusion of EGFP-PDE6C on disc membranes investigated with fluorescence recovery after photobleaching was markedly slower than theoretically predicted. The enzymatic characteristics of immunoprecipitated recombinant PDE6C were similar to known properties of the native bovine PDE6C. PDE6C was potently inhibited by the cone-and rod-specific PDE6 ␥-subunits. Thus, transgenic Xenopus laevis is a unique expression system for PDE6 well suited for analysis of the mechanisms of visual diseases linked to PDE6 mutations.Phosphodiesterases of cyclic nucleotides (PDEs) 2 are essential enzymes controlling cellular levels of cAMP and cGMP. Eleven families of PDEs have been identified in mammals on the grounds of sequence homology, substrate selectivity, and regulation (1). Photoreceptor-specific PDEs in rods and cones comprise the sixth PDE family (PDE6) and serve as the effector enzymes in the vertebrate phototransduction cascade (1-5). Rod PDE6 is composed of homologous catalytic ␣-subunit (PDE6A) and ␤-subunit (PDE6B) and two copies of a small inhibitory ␥-subunit (P␥) (3). Cone PDE6 is a catalytic dimer of two identical ␣Ј-subunits (PDE6C) (3). A cone-specific inhibitory P␥-subunit is highly homologous to the rod P␥ (6). In rod photoreceptors, PDE6 is located in the specialized compartments called rod outer segments (ROS), where it associates with disc membranes. The membrane attachment of PDE6 is mediated by farnesylation of the PDE6A C terminus and geranylgeranylation of the PDE6B C terminus (7). In cones, geranylgeranylated PDE6C resides on infoldings of the cone outer segment plasma membrane (8). Following photoexcitation of rod or cone photoreceptor cells, PDE6 is activated by the GTPbound transducin ␣-subunit (G␣ t GTP) that relieves the P␥ inhibition of the enzyme. cGMP hydrolysis by active PDE6 leads to a cellular response due to a closure of cGMP-gated channels in the photoreceptor plasma membrane (2-5).Although PDE6 plays a prominent role in vertebrate vision, the structure-function relationships of PDE6 are poorly understood in comparison with other key phototransduction proteins. The lack of an expression system for PDE6 has become a major impediment for PDE6 research. Importantly, an expression system for PDE6 is required to elucidate the mechanisms of visua...

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Beyond Counting Photons: Trials and Trends in Vertebrate Visual Transduction

Cited by 225 publications

References 200 publications

Monomeric G protein-coupled receptor rhodopsin in solution activates its G protein transducin at the diffusion limit

Monomeric G protein-coupled receptor rhodopsin in solution activates its G protein transducin at the diffusion limit

Nuclear entry of a cGMP-dependent kinase converts transient into long-lasting olfactory adaptation

Characterization of Human Cone Phosphodiesterase-6 Ectopically Expressed in Xenopus laevis Rods

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