Skip to main content

The vertebrate phototransduction cascade: amplification and termination mechanisms

  • Chapter
  • First Online:

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 154))

Abstract

The biochemical cascade which transduces light into a neuronal signal in retinal photoreceptors is a heterotrimeric GTP-binding protein (G protein) signaling pathway called phototransduction. Works from psychophysicists, electrophysiologists, biochemists, and geneticists over several decades have come together to shape our understanding of how photon absorption leads to photoreceptor membrane hyperpolarization. The insights of phototransduction provide the foundation for a mechanistic account of signaling from many other G protein-coupled receptors (GPCR) found throughout nature. The application of reverse genetic techniques has strengthened many historic findings and helped to describe this pathway at greater molecular details. However, many important questions remain to be answered.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

AFM:

Atomic force microscopy

Arr−/− :

Homozygous arrestin knockout

BAPTA:

1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid

cGMP:

3′,5′ Cyclic guanosine monophosphate

CNBD:

Cyclic nucleotide binding domain

CNG:

Cyclic nucleotide-gated

DEP:

Disheveled, EGL-10, Pleckstrin

ERG:

Electroretinography

EM:

Electron microscopy

GDP:

Guanosine diphosphate

GMP:

Guanosine monophosphate

GTP:

Guanosine triphosphate

GPCR:

G protein-coupled receptor

GC:

Guanylate cyclase

GCAP:

Guanylate cyclase-activating protein

GCAP−/− :

Homozygous GCAP knockout

GAP:

GTPase-accelerating protein

GRK:

G protein-coupled receptor kinase

GGL:

G protein γ-like

GTPγS:

Guanosine-5′-(γ-thio)-triphosphate

K m :

Michaelis–Menten constant

MUV:

Mouse ultraviolet visual pigment

NCKX:

Na+/Ca2+,K+ exchanger

PDE:

Phosphodiesterase

P*:

Activated phosphodiesterase

R:

Rhodopsin

R*:

Metarhodopsin II (activated form of rhodopsin)

RCSB:

Research Collaboratory for Structural Bioinformatics

RK−/− :

Homozygous rhodopsin kinase knockout

Rv−/− :

Recoverin knockout

Rho+/− :

Heterozygous rhodopsin knockout

R9AP:

RGS9 anchoring protein

RGS:

Regulator of G protein signaling

RNA:

Ribonucleic acid

SB:

Schiff base

SW:

Switch region

T:

Heterotrimeric transducin

T*:

Activated transducin

τD :

Dominant time constant of recovery

τrec :

Recovery constant in dim flash response

V max :

Maximal rate of an enzymatic reaction

References

  • Ala-Laurila P, Donner K, Koskelainen A (2004) Thermal activation and photoactivation of visual pigments. Biophys J 86:3653−3662

    PubMed  CAS  Google Scholar 

  • Angleson JK, Wensel TG (1993) A GTPase-accelerating factor for transducin, distinct from its effector cGMP phosphodiesterase, in rod outer segment membranes. Neuron 11:939−949

    PubMed  CAS  Google Scholar 

  • Aris L, Gilchrist A, Rens-Domiano S, Meyer C, Schatz PJ, Dratz EA, Hamm HE (2001) Structural requirements for the stabilization of metarhodopsin II by the C terminus of the alpha subunit of transducin. J Biol Chem 276:2333−2339

    PubMed  CAS  Google Scholar 

  • Arshavsky V, Bownds MD (1992) Regulation of deactivation of photoreceptor G-protein by its target enzyme and cGMP. Nature 357:416−417

    PubMed  Google Scholar 

  • Baehr W, Devlin MJ, Applebury ML (1979) Isolation and characterization of cGMP phosphodiesterase from bovine rod outer segments. J Biol Chem 254:11669−11677

    PubMed  CAS  Google Scholar 

  • Balasubramanian N, Levay K, Keren-Raifman T, Faurobert E, Slepak VZ (2001) Phosphorylation of the regulator of G-protein signaling RGS9-1 by protein kinase A is a potential mechanism of light- and Ca2+-mediated regulation of G-protein function in photoreceptors. Biochemistry 40:12619−12627

    PubMed  CAS  Google Scholar 

  • Barlow RB, Birge RR, Kaplan E, Tallent JR (1993) On the molecular origin of photoreceptor noise. Nature 366:64−66

    PubMed  CAS  Google Scholar 

  • Baumann C (1976) The formation of metarhodospin380 in the retinal rods of the frog. J Physiol 259:357−366

    CAS  Google Scholar 

  • Baylor D (1996) How photons start vision. Proc Natl Acad Sci U S A 93:560−565

    PubMed  CAS  Google Scholar 

  • Baylor DA (1987) Photoreceptor signals and vision. Proctor lecture. Invest Ophthalmol Vis Sci 28:34−49

    PubMed  CAS  Google Scholar 

  • Baylor DA, Nunn BJ, Schnapf JL (1984) The photocurrent, noise and spectral sensitivity of rods of the monkey Macaca fascicularis. J Physiol 357:575−607

    CAS  Google Scholar 

  • Birge RR, Knox BE (2003) Perspectives on the counterion switch-induced photoactivation of the G-protein-coupled receptor rhodopsin. Proc Natl Acad Sci U S A 100:9105−9107

    PubMed  CAS  Google Scholar 

  • Bortoff A (1964) Localization of slow potential responses in the Necturus retina. Vision Res 4:627−635

    PubMed  CAS  Google Scholar 

  • Bourne HR, Stryer L (1992) G-proteins. The target sets the tempo. Nature 358:541−543

    PubMed  CAS  Google Scholar 

  • Bulenger S, Marullo S, Bouvier M (2005) Emerging role of homo- and heterodimerization in G-protein-coupled receptor biosynthesis and maturation. Trends Pharmacol Sci 26:131−137

    PubMed  CAS  Google Scholar 

  • Burns ME, Baylor DA (2001) Activation, deactivation, and adaptation in vertebrate photoreceptor cells. Annu Rev Neurosci 24:779−805

    PubMed  CAS  Google Scholar 

  • Burns ME, Mendez A, Chen J, Baylor DA (2002) Dynamics of cyclic GMP synthesis in retinal rods. Neuron 36:81−91

    PubMed  CAS  Google Scholar 

  • Cai K, Itoh Y, Khorana HG (2001) Mapping of contact sites in complex formation between transducin and light-activated rhodopsin by covalent crosslinking: use of a photoactivatable reagent. Proc Natl Acad Sci U S A 98:4877−4882

    PubMed  CAS  Google Scholar 

  • Calvert PD, Makino CL (2002) The time course of light adaptation in vertebrate retinal rods. Adv Exp Med Biol 514:37−60

    PubMed  CAS  Google Scholar 

  • Calvert PD, Govardovskii VI, Krasnoperova N, Anderson RE, Lem J, Makino CL (2001) Membrane protein diffusion sets the speed of rod phototransduction. Nature 411:90−94

    PubMed  CAS  Google Scholar 

  • Chabre M, Cone R, Saibil H (2003) Biophysics: is rhodopsin dimeric in native retinal rods? Nature 426:30−31; discussion 31

    PubMed  CAS  Google Scholar 

  • Chen CK (2002) Recoverin and rhodopsin kinase. Adv Exp Med Biol 514:101−107

    PubMed  CAS  Google Scholar 

  • Chen CK, Inglese J, Lefkowitz RJ, Hurley JB (1995a) Ca(2+)-dependent interaction of recoverin with rhodopsin kinase. J Biol Chem 270:18060−18066

    PubMed  CAS  Google Scholar 

  • Chen CK, Burns ME, Spencer M, Niemi GA, Chen J, Hurley JB, Baylor DA, Simon MI (1999) Abnormal photoresponses and light-induced apoptosis in rods lacking rhodopsin kinase. Proc Natl Acad Sci U S A 96:3718−3722

    PubMed  CAS  Google Scholar 

  • Chen CK, Burns ME, He W, Wensel TG, Baylor DA, Simon MI (2000) Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating-protein RGS9-1. Nature 403:557−560

    PubMed  CAS  Google Scholar 

  • Chen CK, Zhang K, Church-Kopish J, Huang W, Zhang H, Chen YJ, Frederick JM, Baehr W (2001) Characterization of human GRK7 as a potential cone opsin kinase. Mol Vis 7:305−313

    PubMed  CAS  Google Scholar 

  • Chen CK, Eversole-Cire P, Zhang H, Mancino V, Chen YJ, He W, Wensel TG, Simon MI (2003) Instability of GGL domain-containing RGS proteins in mice lacking the G-protein beta-subunit Gbeta5. Proc Natl Acad Sci U S A 100:6604−6609

    PubMed  CAS  Google Scholar 

  • Chen J, Makino CL, Peachey NS, Baylor DA, Simon MI (1995b) Mechanisms of rhodopsin inactivation in vivo as revealed by a COOH-terminal truncation mutant. Science 267:374−377

    PubMed  CAS  Google Scholar 

  • Chen TY, Peng YW, Dhallan RS, Ahamed B, Reed RR, Yau KW (1993) A new subunit of the cyclic nucleotide-gated cation channel in retinal rods. Nature 362:764−767

    PubMed  CAS  Google Scholar 

  • Cideciyan AV, Zhao X, Nielsen L, Khani SC, Jacobson SG, Palczewski K (1998) Null mutation in the rhodopsin kinase gene slows recovery kinetics of rod and cone phototransduction in man. Proc Natl Acad Sci U S A 95:328−333

    PubMed  CAS  Google Scholar 

  • Cone RA (1972) Rotational diffusion of rhodopsin in the visual receptor membrane. Nat New Biol 236:39−43

    PubMed  CAS  Google Scholar 

  • Cook NJ, Molday LL, Reid D, Kaupp UB, Molday RS (1989) The cGMP-gated channel of bovine rod photoreceptors is localized exclusively in the plasma membrane. J Biol Chem 264:6996−6999

    PubMed  CAS  Google Scholar 

  • Cooper A (1979) Energy uptake in the first step of visual excitation. Nature 282:531−533

    PubMed  CAS  Google Scholar 

  • Cote RH (2004) Characteristics of photoreceptor PDE (PDE6): similarities and differences to PDE5. Int J Impot Res 16 Suppl 1:S28−33

    Google Scholar 

  • Cowan CW, Fariss RN, Sokal I, Palczewski K, Wensel TG (1998) High expression levels in cones of RGS9, the predominant GTPase accelerating-protein of rods. Proc Natl Acad Sci U S A 95:5351−5356

    PubMed  CAS  Google Scholar 

  • Craft CM, Whitmore DH (1995) The arrestin superfamily: cone arrestins are a fourth family. FEBS Lett 362:247−255

    PubMed  CAS  Google Scholar 

  • Crescitelli F (1984) The gecko visual pigment: the dark exchange of chromophore. Vision Res 24:1551−1553

    PubMed  CAS  Google Scholar 

  • Dizhoor AM, Ray S, Kumar S, Niemi G, Spencer M, Brolley D, Walsh KA, Philipov PP, Hurley JB, Stryer L (1991) Recoverin: a calcium sensitive activator of retinal rod guanylate cyclase. Science 251:915−918

    PubMed  CAS  Google Scholar 

  • Dizhoor AM, Olshevskaya EV, Henzel WJ, Wong SC, Stults JT, Ankoudinova I, Hurley JB (1995) Cloning, sequencing, and expression of a 24-kDa Ca(2+)-binding-protein activating photoreceptor guanylyl cyclase. J Biol Chem 270:25200−25206

    PubMed  CAS  Google Scholar 

  • Dryja TP (2000) Molecular genetics of Oguchi disease, fundus albipunctatus, and other forms of stationary night blindness: LVII Edward Jackson Memorial Lecture. Am J Ophthalmol 130:547−563

    PubMed  CAS  Google Scholar 

  • Dukkipati A, Kusnetzow A, Babu KR, Ramos L, Singh D, Knox BE, Birge RR (2002) Phototransduction by vertebrate ultraviolet visual pigments: protonation of the retinylidene Schiff base following photobleaching. Biochemistry 41:9842−9851

    PubMed  CAS  Google Scholar 

  • Ebrey TG (2000) pKa of the protonated Schiff base of visual pigments. Methods Enzymol 315:196−207

    PubMed  CAS  Google Scholar 

  • Edwards PC, Li J, Burghammer M, McDowell JH, Villa C, Hargrave PA, Schertler GF (2004) Crystals of native and modified bovine rhodopsins and their heavy atom derivatives. J Mol Biol 343:1439−1450

    PubMed  CAS  Google Scholar 

  • Erickson MA, Lagnado L, Zozulya S, Neubert TA, Stryer L, Baylor DA (1998) The effect of recombinant recoverin on the photoresponse of truncated rod photoreceptors. Proc Natl Acad Sci U S A 95:6474−6479

    PubMed  CAS  Google Scholar 

  • Fesenko EE, Kolesnikov SS, Lyubarsky AL (1985) Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment. Nature 313:310−313

    PubMed  CAS  Google Scholar 

  • Field GD, Rieke F (2002) Mechanisms regulating variability of the single photon responses of mammalian rod photoreceptors. Neuron 35:733−747

    PubMed  CAS  Google Scholar 

  • Fotiadis D, Liang Y, Filipek S, Saperstein DA, Engel A, Palczewski K (2003) Atomic-force microscopy: rhodopsin dimers in native disc membranes. Nature 421:127−128

    PubMed  CAS  Google Scholar 

  • Fuchs S, Nakazawa M, Maw M, Tamai M, Oguchi Y, Gal A (1995) A homozygous 1-base pair deletion in the arrestin gene is a frequent cause of Oguchi disease in Japanese. Nat Genet 10:360−362

    PubMed  CAS  Google Scholar 

  • Fung BK, Hurley JB, Stryer L (1981) Flow of information in the light-triggered cyclic nucleotide cascade of vision. Proc Natl Acad Sci U S A 78:152−156

    PubMed  CAS  Google Scholar 

  • Gold SJ, Heifets BD, Pudiak CM, Potts BW, Nestler EJ (2002) Regulation of regulators of G-protein signaling mRNA expression in rat brain by acute and chronic electroconvulsive seizures. J Neurochem 82:828−838

    PubMed  CAS  Google Scholar 

  • Gray-Keller MP, Detwiler PB (1994) The calcium feedback signal in the phototransduction cascade of vertebrate rods. Neuron 13:849−861

    PubMed  CAS  Google Scholar 

  • Gray-Keller MP, Polans AS, Palczewski K, Detwiler PB (1993) The effect of recoverin-like calcium-binding-proteins on the photoresponse of retinal rods. Neuron 10:523−531

    PubMed  CAS  Google Scholar 

  • Hagins WA, Yoshikami S (1974) Proceedings: a role for Ca2+ in excitation of retinal rods and cones. Exp Eye Res 18:299−305

    PubMed  CAS  Google Scholar 

  • Hardie RC (2001) Phototransduction in Drosophila melanogaster. J Exp Biol 204:3403−3409

    PubMed  CAS  Google Scholar 

  • He W, Cowan CW, Wensel TG (1998) RGS9, a GTPase accelerator for phototransduction. Neuron 20:95−102

    PubMed  Google Scholar 

  • Hecht SS, Pirenne MH (1942) Energy, quanta, and vision. J Gen Physiol 25:819−840

    PubMed  CAS  Google Scholar 

  • Horner TJ, Osawa S, Schaller MD, Weiss ER (2005) Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase attenuates their enzymatic activities. J Biol Chem 280:28241−28250

    PubMed  CAS  Google Scholar 

  • Hsu YT, Molday RS (1993) Modulation of the cGMP-gated channel of rod photoreceptor cells by calmodulin. Nature 361:76−79

    PubMed  CAS  Google Scholar 

  • Hu G, Wensel TG (2002) R9AP, a membrane anchor for the photoreceptor GTPase accelerating-protein, RGS9-1. Proc Natl Acad Sci U S A 99:9755−9760

    PubMed  CAS  Google Scholar 

  • Hu G, Jang GF, Cowan CW, Wensel TG, Palczewski K (2001) Phosphorylation of RGS9-1 by an endogenous protein kinase in rod outer segments. J Biol Chem 276:22287−22295

    PubMed  CAS  Google Scholar 

  • Hubbell WL, Cafiso DS, Altenbach C (2000) Identifying conformational changes with site-directed spin labeling. Nat Struct Biol 7:735−739

    PubMed  CAS  Google Scholar 

  • Hubbell WL, Altenbach C, Hubbell CM, Khorana HG (2003) Rhodopsin structure, dynamics, and activation: a perspective from crystallography, site-directed spin labeling, sulfhydryl reactivity, and disulfide cross-linking. Adv Protein Chem 63:243−290

    PubMed  CAS  Google Scholar 

  • Hurley JB, Chen J (2001) Evaluation of the contributions of recoverin and GCAPs to rod photoreceptor light adaptation and recovery to the dark state. Prog Brain Res 131:395−405

    PubMed  CAS  Google Scholar 

  • Hurley JB, Stryer L (1982) Purification and characterization of the gamma regulatory subunit of the cyclic GMP phosphodiesterase from retinal rod outer segments. J Biol Chem 257:11094−11099

    PubMed  CAS  Google Scholar 

  • Hurley JB, Dizhoor AM, Ray S, Stryer L (1993) Recoverin's role: conclusion withdrawn. Science 260:740

    PubMed  CAS  Google Scholar 

  • Imai H, Terakita A, Tachibanaki S, Imamoto Y, Yoshizawa T, Shichida Y (1997) Photochemical and biochemical properties of chicken blue-sensitive cone visual pigment. Biochemistry 36:12773−12779

    PubMed  CAS  Google Scholar 

  • Jastrzebska B, Maeda T, Zhu L, Fotiadis D, Filipek S, Engel A, Stenkamp RE, Palczewski K (2004) Functional characterization of rhodopsin monomers and dimers in detergents. J Biol Chem 279:54663−54675

    PubMed  CAS  Google Scholar 

  • Jeon CJ, Strettoi E, Masland RH (1998) The major cell populations of the mouse retina. J Neurosci 18:8936−8946

    PubMed  CAS  Google Scholar 

  • Johnson S, Michaelides M, Aligianis IA, Ainsworth JR, Mollon JD, Maher ER, Moore AT, Hunt DM (2004) Achromatopsia caused by novel mutations in both CNGA3 and CNGB3. J Med Genet 41:e20

    PubMed  CAS  Google Scholar 

  • Kang K, Bauer PJ, Kinjo TG, Szerencsei RT, Bonigk W, Winkfein RJ, Schnetkamp PP (2003) Assembly of retinal rod or cone Na(+)/Ca(2+)-K(+) exchanger oligomers with cGMP-gated channel subunits as probed with heterologously expressed cDNAs. Biochemistry 42:4593−4600

    PubMed  CAS  Google Scholar 

  • Kaupp UB, Hanke W, Simmoteit R, Luhring H (1988) Electrical and biochemical properties of the cGMP-gated cation channel from rod photoreceptors. Cold Spring Harb Symp Quant Biol 53:407−415

    PubMed  CAS  Google Scholar 

  • Kaupp UB, Niidome T, Tanabe T, Terada S, Bonigk W, Stuhmer W, Cook NJ, Kangawa K, Matsuo H, Hirose T et al. (1989) Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel. Nature 342:762−766

    PubMed  CAS  Google Scholar 

  • Kawamura S (1993) Rhodopsin phosphorylation as a mechanism of cyclic GMP phosphodiesterase regulation by S-modulin. Nature 362:855−857

    PubMed  CAS  Google Scholar 

  • Kefalov V, Fu Y, Marsh-Armstrong N, Yau KW (2003) Role of visual pigment properties in rod and cone phototransduction. Nature 425:526−531

    PubMed  CAS  Google Scholar 

  • Kefalov VJ, Estevez ME, Kono M, Goletz PW, Crouch RK, Cornwall MC, Yau KW (2005) Breaking the covalent bond—a pigment property that contributes to desensitization in cones. Neuron 46:879−890

    PubMed  CAS  Google Scholar 

  • Keresztes G, Martemyanov KA, Krispel CM, Mutai H, Yoo PJ, Maison SF, Burns ME, Arshavsky VY, Heller S (2004) Absence of the RGS9.Gbeta5 GTPase-activating complex in photoreceptors of the R9AP knockout mouse. J Biol Chem 279:1581−1584

    PubMed  CAS  Google Scholar 

  • Klein-Seetharaman J, Hwa J, Cai K, Altenbach C, Hubbell WL, Khorana HG (1999) Single-cysteine substitution mutants at amino acid positions 55−75, the sequence connecting the cytoplasmic ends of helices I and II in rhodopsin: reactivity of the sulfhydryl groups and their derivatives identifies a tertiary structure that changes upon light-activation. Biochemistry 38:7938−7944

    PubMed  CAS  Google Scholar 

  • Klenchin VA, Calvert PD, Bownds MD (1995) Inhibition of rhodopsin kinase by recoverin. Further evidence for a negative feedback system in phototransduction. J Biol Chem 270:16147−16152

    PubMed  CAS  Google Scholar 

  • Koch KW, Stryer L (1988) Highly cooperative feedback control of retinal rod guanylate cyclase by calcium ions. Nature 334:64−66

    PubMed  CAS  Google Scholar 

  • Korschen HG, Illing M, Seifert R, Sesti F, Williams A, Gotzes S, Colville C, Muller F, Dose A, Godde M et al. (1995) A 240 kDa protein represents the complete beta subunit of the cyclic nucleotide-gated channel from rod photoreceptor. Neuron 15:627−636

    PubMed  CAS  Google Scholar 

  • Koutalos Y, Nakatani K, Tamura T, Yau KW (1995a) Characterization of guanylate cyclase activity in single retinal rod outer segments. J Gen Physiol 106:863−890

    PubMed  CAS  Google Scholar 

  • Koutalos Y, Nakatani K, Yau KW (1995b) The cGMP-phosphodiesterase and its contribution to sensitivity regulation in retinal rods. J Gen Physiol 106:891−921

    PubMed  CAS  Google Scholar 

  • Krispel CM, Chen CK, Simon MI, Burns ME (2003a) Novel form of adaptation in mouse retinal rods speeds recovery of phototransduction. J Gen Physiol 122:703−712

    PubMed  CAS  Google Scholar 

  • Krispel CM, Chen CK, Simon MI, Burns ME (2003b) Prolonged photoresponses and defective adaptation in rods of Gbeta5−/− mice. J Neurosci 23:6965−6971

    PubMed  CAS  Google Scholar 

  • Kusnetzow AK, Dukkipati A, Babu KR, Ramos L, Knox BE, Birge RR (2004) Vertebrate ultraviolet visual pigments: protonation of the retinylidene Schiff base and a counterion switch during photoactivation. Proc Natl Acad Sci U S A 101:941−946

    PubMed  CAS  Google Scholar 

  • Lagnado L, Baylor D (1992) Signal flow in visual transduction. Neuron 8:995−1002

    PubMed  CAS  Google Scholar 

  • Lamb TD, Baylor DA, Yau KW (1979) The membrane current of single rod outer segments. Vision Res 19:385

    PubMed  CAS  Google Scholar 

  • Lambrecht HG, Koch KW (1991) A 26 kd calcium binding-protein from bovine rod outer segments as modulator of photoreceptor guanylate cyclase. EMBO J 10:793−798

    PubMed  CAS  Google Scholar 

  • Lambright DG, Sondek J, Bohm A, Skiba NP, Hamm HE, Sigler PB (1996) The 2.0 A crystal structure of a heterotrimeric G-protein. Nature 379:311−319

    PubMed  CAS  Google Scholar 

  • Langlois G, Chen CK, Palczewski K, Hurley JB, Vuong TM (1996) Responses of the phototransduction cascade to dim light. Proc Natl Acad Sci U S A 93:4677−4682

    PubMed  CAS  Google Scholar 

  • Lee RH, Navon SE, Brown BM, Fung BK, Lolley RN (1988) Characterization of a phosphodiesterase-immunoreactive polypeptide from rod photoreceptors of developing rd mouse retinas. Invest Ophthalmol Vis Sci 29:1021−1027

    PubMed  CAS  Google Scholar 

  • Leskov IB, Klenchin VA, Handy JW, Whitlock GG, Govardovskii VI, Bownds MD, Lamb TD, Pugh EN Jr, Arshavsky VY (2000) The gain of rod phototransduction: reconciliation of biochemical and electrophysiological measurements. Neuron 27:525−537

    PubMed  CAS  Google Scholar 

  • Lewis JW, Kliger DS (1992) Photointermediates of visual pigments. J Bioenerg Biomembr 24:201−210

    PubMed  CAS  Google Scholar 

  • Li TS, Volpp K, Applebury ML (1990) Bovine cone photoreceptor cGMP phosphodiesterase structure deduced from a cDNA clone. Proc Natl Acad Sci U S A 87:293−297

    PubMed  CAS  Google Scholar 

  • Liang J, Steinberg G, Livnah N, Sheves M, Ebrey TG, Tsuda M (1994) The pKa of the protonated Schiff bases of gecko cone and octopus visual pigments. Biophys J 67:848−854

    PubMed  CAS  Google Scholar 

  • Liang Y, Fotiadis D, Maeda T, Maeda A, Modzelewska A, Filipek S, Saperstein DA, Engel A, Palczewski K (2004) Rhodopsin signaling and organization in heterozygote rhodopsin knockout mice. J Biol Chem 279:48189−48196

    PubMed  CAS  Google Scholar 

  • Lin SW, Sakmar TP, Franke RR, Khorana HG, Mathies RA (1992) Resonance Raman microprobe spectroscopy of rhodopsin mutants: effect of substitutions in the third transmembrane helix. Biochemistry 31:5105−5111

    PubMed  CAS  Google Scholar 

  • Lyubarsky A, Nikonov S, Pugh EN Jr (1996) The kinetics of inactivation of the rod phototransduction cascade with constant Ca2+i. J Gen Physiol 107:19−34

    PubMed  CAS  Google Scholar 

  • Lyubarsky AL, Chen C, Simon MI, Pugh EN Jr (2000) Mice lacking G-protein receptor kinase 1 have profoundly slowed recovery of cone-driven retinal responses. J Neurosci 20:2209−2217

    PubMed  CAS  Google Scholar 

  • Lyubarsky AL, Naarendorp F, Zhang X, Wensel T, Simon MI, Pugh EN Jr (2001) RGS9-1 is required for normal inactivation of mouse cone phototransduction. Mol Vis 7:71−78

    PubMed  CAS  Google Scholar 

  • Makino CL, Dodd RL, Chen J, Burns ME, Roca A, Simon MI, Baylor DA (2004) Recoverin regulates light-dependent phosphodiesterase activity in retinal rods. J Gen Physiol 123:729−741

    PubMed  CAS  Google Scholar 

  • Makino ER, Handy JW, Li T, Arshavsky VY (1999) The GTPase activating factor for transducin in rod photoreceptors is the complex between RGS9 and type 5 G-protein beta subunit. Proc Natl Acad Sci U S A 96:1947−1952

    PubMed  CAS  Google Scholar 

  • Martemyanov KA, Lishko PV, Calero N, Keresztes G, Sokolov M, Strissel KJ, Leskov IB, Hopp JA, Kolesnikov AV, Chen CK, Lem J, Heller S, Burns ME, Arshavsky VY (2003) The DEP domain determines subcellular targeting of the GTPase activating protein RGS9 in vivo. J Neurosci 23:10175−10181

    PubMed  CAS  Google Scholar 

  • Matsumoto H, Tokunaga F, Yoshizawa T (1975) Accessibility of the iodopsin chromophore. Biochim Biophys Acta 404:300−308

    PubMed  CAS  Google Scholar 

  • McBee JK, Palczewski K, Baehr W, Pepperberg DR (2001) Confronting complexity: the interlink of phototransduction and retinoid metabolism in the vertebrate retina. Prog Retin Eye Res 20:469−529

    PubMed  CAS  Google Scholar 

  • Mendez A, Chen J (2002) Mouse models to study GCAP functions in intact photoreceptors. Adv Exp Med Biol 514:361−388

    PubMed  CAS  Google Scholar 

  • Mendez A, Burns ME, Roca A, Lem J, Wu LW, Simon MI, Baylor DA, Chen J (2000) Rapid and reproducible deactivation of rhodopsin requires multiple phosphorylation sites. Neuron 28:153−164

    PubMed  CAS  Google Scholar 

  • Mirnics K, Middleton FA, Stanwood GD, Lewis DA, Levitt P (2001) Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. Mol Psychiatry 6:293−301

    PubMed  CAS  Google Scholar 

  • Mou H, Cote RH (2001) The catalytic and GAF domains of the rod cGMP phosphodiesterase (PDE6) heterodimer are regulated by distinct regions of its inhibitory gamma subunit. J Biol Chem 276:27527−27534

    PubMed  CAS  Google Scholar 

  • Nakatani K, Yau KW (1988) Guanosine 3',5'-cyclic monophosphate-activated conductance studied in a truncated rod outer segment of the toad. J Physiol 395:731−753

    CAS  Google Scholar 

  • Nakatani K, Chen C, Yau KW, Koutalos Y (2002) Calcium and phototransduction. Adv Exp Med Biol 514:1−20

    PubMed  CAS  Google Scholar 

  • Nathans J (1990) Determinants of visual pigment absorbance: identification of the retinylidene Schiff's base counterion in bovine rhodopsin. Biochemistry 29:9746−9752

    PubMed  CAS  Google Scholar 

  • Natochin M, Granovsky AE, Muradov KG, Artemyev NO (1999) Roles of the transducin alpha-subunit alpha4-helix/alpha4-beta6 loop in the receptor and effector interactions. J Biol Chem 274:7865−7869

    PubMed  CAS  Google Scholar 

  • Natochin M, Muradov KG, McEntaffer RL, Artemyev NO (2000) Rhodopsin recognition by mutant G(s)alpha containing C-terminal residues of transducin. J Biol Chem 275:2669−2675

    PubMed  CAS  Google Scholar 

  • Nishiguchi KM, Sandberg MA, Kooijman AC, Martemyanov KA, Pott JW, Hagstrom SA, Arshavsky VY, Berson EL, Dryja TP (2004) Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation. Nature 427:75−78

    PubMed  CAS  Google Scholar 

  • Noel JP, Hamm HE, Sigler PB (1993) The 2.2 A crystal structure of transducin-alpha complexed with GTP gamma S. Nature 366:654−663

    PubMed  CAS  Google Scholar 

  • Osorio D, Nilsson DE (2004) Visual pigments: trading noise for fast recovery. Curr Biol 14:R1051−1053

    PubMed  CAS  Google Scholar 

  • Otto-Bruc AE, Fariss RN, Van Hooser JP, Palczewski K (1998) Phosphorylation of photolyzed rhodopsin is calcium-insensitive in retina permeabilized by alpha-toxin. Proc Natl Acad Sci U S A 95:15014−15019

    PubMed  CAS  Google Scholar 

  • Palczewski K, Subbaraya I, Gorczyca WA, Helekar BS, Ruiz CC, Ohguro H, Huang J, Zhao X, Crabb JW, Johnson RS et al. (1994) Molecular cloning and characterization of retinal photoreceptor guanylyl cyclase-activating-protein. Neuron 13:395−404

    PubMed  CAS  Google Scholar 

  • Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE et al. (2000) Crystal structure of rhodopsin: A G-protein-coupled receptor. Science 289:739−745

    PubMed  CAS  Google Scholar 

  • Palczewski K, Sokal I, Baehr W (2004) Guanylate cyclase-activating-proteins: structure, function, and diversity. Biochem Biophys Res Commun 322:1123−1130

    PubMed  CAS  Google Scholar 

  • Park PS, Filipek S, Wells JW, Palczewski K (2004) Oligomerization of G-protein-coupled receptors: past, present, and future. Biochemistry 43:15643−15656

    PubMed  CAS  Google Scholar 

  • Pepperberg DR, Cornwall MC, Kahlert M, Hofmann KP, Jin J, Jones GJ, Ripps H (1992) Light-dependent delay in the falling phase of the retinal rod photoresponse. Vis Neurosci 8:9−18

    PubMed  CAS  Google Scholar 

  • Poo M, Cone RA (1974) Lateral diffusion of rhodopsin in the photoreceptor membrane. Nature 247:438−441

    PubMed  CAS  Google Scholar 

  • Preininger AM, Hamm HE (2004) G-protein signaling: insights from new structures. Sci STKE 2004:re3

    Google Scholar 

  • Pugh EN Jr, Lamb TD (1993) Amplification and kinetics of the activation steps in phototransduction. Biochim Biophys Acta 1141:111--149

    Google Scholar 

  • Qin N, Pittler SJ, Baehr W (1992) In vitro isoprenylation and membrane association of mouse rod photoreceptor cGMP phosphodiesterase alpha and beta subunits expressed in bacteria. J Biol Chem 267:8458−8463

    PubMed  CAS  Google Scholar 

  • Rahman Z, Gold SJ, Potenza MN, Cowan CW, Ni YG, He W, Wensel TG, Nestler EJ (1999) Cloning and characterization of RGS9−2: a striatal-enriched alternatively spliced product of the RGS9 gene. J Neurosci 19:2016−2026

    PubMed  CAS  Google Scholar 

  • Ramdas L, Disher RM, Wensel TG (1991) Nucleotide exchange and cGMP phosphodiesterase activation by pertussis toxin inactivated transducin. Biochemistry 30:11637−11645

    PubMed  CAS  Google Scholar 

  • Rieke F, Baylor DA (1998) Origin of reproducibility in the responses of retinal rods to single photons. Biophys J 75:1836−1857

    PubMed  CAS  Google Scholar 

  • Rivolta C, Sharon D, DeAngelis MM, Dryja TP (2002) Retinitis pigmentosa and allied diseases: numerous diseases, genes, and inheritance patterns. Hum Mol Genet 11:1219−1227

    PubMed  CAS  Google Scholar 

  • Robinson PR, Cohen GB, Zhukovsky EA, Oprian DD (1992) Constitutively active mutants of rhodopsin. Neuron 9:719−725

    PubMed  CAS  Google Scholar 

  • Ross EM, Wilkie TM (2000) GTPase-activating-proteins for heterotrimeric G-proteins: regulators of G-protein signaling (RGS) and RGS-like proteins. Annu Rev Biochem 69:795−827

    PubMed  CAS  Google Scholar 

  • Saari JC, Garwin GG, Van Hooser JP, Palczewski K (1998) Reduction of all-trans-retinal limits regeneration of visual pigment in mice. Vision Res 38:1325−1333

    PubMed  CAS  Google Scholar 

  • Sagoo MS, Lagnado L (1997) G-protein deactivation is rate-limiting for shut-off of the phototransduction cascade. Nature 389:392−395

    PubMed  CAS  Google Scholar 

  • Sakmar TP, Franke RR, Khorana HG (1989) Glutamic acid-113 serves as the retinylidene Schiff base counterion in bovine rhodopsin. Proc Natl Acad Sci U S A 86:8309−8313

    PubMed  CAS  Google Scholar 

  • Sakmar TP, Franke RR, Khorana HG (1991) The role of the retinylidene Schiff base counterion in rhodopsin in determining wavelength absorbance and Schiff base pKa. Proc Natl Acad Sci U S A 88:3079−3083

    PubMed  CAS  Google Scholar 

  • Sampath AP, Baylor DA (2002) Molecular mechanism of spontaneous pigment activation in retinal cones. Biophys J 83:184−193

    PubMed  CAS  Google Scholar 

  • Sampath AP, Matthews HR, Cornwall MC, Bandarchi J, Fain GL (1999) Light-dependent changes in outer segment free-Ca2+ concentration in salamander cone photoreceptors. J Gen Physiol 113:267−277

    PubMed  CAS  Google Scholar 

  • Sampath AP, Strissel KJ, Elias R, Arshavsky VY, McGinnis JF, Chen J, Kawamura S, Rieke F, Hurley JB (2005) Recoverin improves rod-mediated vision by enhancing signal transmission in the mouse retina. Neuron 46:413−420

    PubMed  CAS  Google Scholar 

  • Schertler GF, Hargrave PA (1995) Projection structure of frog rhodopsin in two crystal forms. Proc Natl Acad Sci U S A 92:11578−11582

    PubMed  CAS  Google Scholar 

  • Schnapf JL, Nunn BJ, Meister M, Baylor DA (1990) Visual transduction in cones of the monkey Macaca fascicularis. J Physiol 427:681−713

    CAS  Google Scholar 

  • Schoenlein RW, Peteanu LA, Mathies RA, Shank CV (1991) The first step in vision: femtosecond isomerization of rhodopsin. Science 254:412−415

    PubMed  CAS  Google Scholar 

  • Schwarzer A, Schauf H, Bauer PJ (2000) Binding of the cGMP-gated channel to the Na/Ca-K exchanger in rod photoreceptors. J Biol Chem 275:13448−13454

    PubMed  CAS  Google Scholar 

  • Shichida Y, Imai H, Imamoto Y, Fukada Y, Yoshizawa T (1994) Is chicken green-sensitive cone visual pigment a rhodopsin-like pigment? A comparative study of the molecular properties between chicken green and rhodopsin. Biochemistry 33:9040−9044

    PubMed  CAS  Google Scholar 

  • Slepak VZ, Artemyev NO, Zhu Y, Dumke CL, Sabacan L, Sondek J, Hamm HE, Bownds MD, Arshavsky VY (1995) An effector site that stimulates G-protein GTPase in photoreceptors. J Biol Chem 270:14319−14324

    PubMed  CAS  Google Scholar 

  • Smith WC, Milam AH, Dugger D, Arendt A, Hargrave PA, Palczewski K (1994) A splice variant of arrestin. Molecular cloning and localization in bovine retina. J Biol Chem 269:15407−15410

    PubMed  CAS  Google Scholar 

  • Sondek J, Lambright DG, Noel JP, Hamm HE, Sigler PB (1994) GTPase mechanism of Gproteins from the 1.7-A crystal structure of transducin alpha-GDP-AIF-4. Nature 372:276−279

    PubMed  CAS  Google Scholar 

  • Sprang SR (1997) G-protein mechanisms: insights from structural analysis. Annu Rev Biochem 66:639−678

    PubMed  CAS  Google Scholar 

  • Steinberg G, Ottolenghi M, Sheves M (1993) pKa of the protonated Schiff base of bovine rhodopsin. A study with artificial pigments. Biophys J 64:1499−1502

    PubMed  CAS  Google Scholar 

  • Struthers M, Yu H, Oprian DD (2000) G-protein-coupled receptor activation: analysis of a highly constrained, “straitjacketed” rhodopsin. Biochemistry 39:7938−7942

    PubMed  CAS  Google Scholar 

  • Stryer L (1991) Visual excitation and recovery. J Biol Chem 266:10711−10714

    PubMed  CAS  Google Scholar 

  • Suda K, Filipek S, Palczewski K, Engel A, Fotiadis D (2004) The supramolecular structure of the GPCR rhodopsin in solution and native disc membranes. Mol Membr Biol 21:435−446

    PubMed  CAS  Google Scholar 

  • Tachibanaki S, Arinobu D, Shimauchi-Matsukawa Y, Tsushima S, Kawamura S (2005) Highly effective phosphorylation by G-protein-coupled receptor kinase 7 of light-activated visual pigment in cones. Proc Natl Acad Sci U S A 102:9329−9334

    PubMed  CAS  Google Scholar 

  • Taylor WR, Smith RG (2004) Transmission of scotopic signals from the rod to rod-bipolar cell in the mammalian retina. Vision Res 44:3269−3276

    PubMed  CAS  Google Scholar 

  • Tomita T, Kaneko A, Murakami M, Pautler EL (1967) Spectral response curves of single cones in the carp. Vision Res 7:519−531

    PubMed  CAS  Google Scholar 

  • Travis GH (2005) DISCO! Dissociation of cone opsins: the fast and noisy life of cones explained. Neuron 46:840−842

    PubMed  CAS  Google Scholar 

  • Traynor JR, Neubig RR (2005) Regulators of G-protein signaling and drugs of abuse. Mol Interv 5:30−41

    PubMed  CAS  Google Scholar 

  • Tsang SH, Burns ME, Calvert PD, Gouras P, Baylor DA, Goff SP, Arshavsky VY (1998) Role for the target enzyme in deactivation of photoreceptor G-protein in vivo. Science 282:117−121

    PubMed  CAS  Google Scholar 

  • Vuong TM, Chabre M, Stryer L (1984) Millisecond activation of transducin in the cyclic nucleotide cascade of vision. Nature 311:659−661

    PubMed  CAS  Google Scholar 

  • Wassle H (2004) Parallel processing in the mammalian retina. Nat Rev Neurosci 5:747−757

    PubMed  Google Scholar 

  • Watson AJ, Katz A, Simon MI (1994) A fifth member of the mammalian G-protein beta-subunit family. Expression in brain and activation of the beta 2 isotype of phospholipase C. J Biol Chem 269:22150−22156

    PubMed  CAS  Google Scholar 

  • Watson AJ, Aragay AM, Slepak VZ, Simon MI (1996) A novel form of the G-protein beta subunit Gbeta5 is specifically expressed in the vertebrate retina. J Biol Chem 271:28154−28160

    PubMed  CAS  Google Scholar 

  • Weiss ER, Ducceschi MH, Horner TJ, Li A, Craft CM, Osawa S (2001) Species-specific differences in expression of G-protein-coupled receptor kinase (GRK) 7 and GRK1 in mammalian cone photoreceptor cells: implications for cone cell phototransduction. J Neurosci 21:9175−9184

    PubMed  CAS  Google Scholar 

  • Weitz D, Ficek N, Kremmer E, Bauer PJ, Kaupp UB (2002) Subunit stoichiometry of the CNG channel of rod photoreceptors. Neuron 36:881−889

    PubMed  CAS  Google Scholar 

  • Wilden U, Hall SW, Kuhn H (1986) Phosphodiesterase activation by photoexcited rhodopsin is quenched when rhodopsin is phosphorylated and binds the intrinsic 48-kDa protein of rod outer segments. Proc Natl Acad Sci U S A 83:1174−1178

    PubMed  CAS  Google Scholar 

  • Woodruff ML, Sampath AP, Matthews HR, Krasnoperova NV, Lem J, Fain GL (2002) Measurement of cytoplasmic calcium concentration in the rods of wild-type and transducin knock-out mice. J Physiol 542:843−854

    CAS  Google Scholar 

  • Xu J, Dodd RL, Makino CL, Simon MI, Baylor DA, Chen J (1997) Prolonged photoresponses in transgenic mouse rods lacking arrestin. Nature 389:505−509

    PubMed  CAS  Google Scholar 

  • Yamamoto S, Sippel KC, Berson EL, Dryja TP (1997) Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness. Nat Genet 15:175−178

    PubMed  CAS  Google Scholar 

  • Yamazaki M, Li N, Bondarenko VA, Yamazaki RK, Baehr W, Yamazaki A (2002) Binding of cGMP to GAF domains in amphibian rod photoreceptor cGMP phosphodiesterase (PDE). Identification of GAF domains in PDE alphabeta subunits and distinct domains in the PDE gamma subunit involved in stimulation of cGMP binding to GAF domains. J Biol Chem 277:40675−40686

    PubMed  CAS  Google Scholar 

  • Yau KW, Nakatani K (1985a) Light-induced reduction of cytoplasmic free calcium in retinal rod outer segment. Nature 313:579−582

    PubMed  CAS  Google Scholar 

  • Yau KW, Nakatani K (1985b) Light-suppressible, cyclic GMP-sensitive conductance in the plasma membrane of a truncated rod outer segment. Nature 317:252−255

    PubMed  CAS  Google Scholar 

  • Yau KW, Lamb TD, Matthews G, Baylor DA (1979a) Current fluctuations across single rod outer segments. Vision Res 19:387−390

    PubMed  CAS  Google Scholar 

  • Yau KW, Matthews G, Baylor DA (1979b) Thermal activation of the visual transduction mechanism in retinal rods. Nature 279:806−807

    PubMed  CAS  Google Scholar 

  • Zhang K, Howes KA, He W, Bronson JD, Pettenati MJ, Chen C, Palczewski K, Wensel TG, Baehr W (1999) Structure, alternative splicing, and expression of the human RGS9 gene. Gene 240:23−34

    CAS  Google Scholar 

  • Zhang X, Wensel TG, Kraft TW (2003) GTPase regulators and photoresponses in cones of the eastern chipmunk. J Neurosci 23:1287−1297

    PubMed  CAS  Google Scholar 

  • Zhao X, Haeseleer F, Fariss RN, Huang J, Baehr W, Milam AH, Palczewski K (1997) Molecular cloning and localization of rhodopsin kinase in the mammalian pineal. Vis Neurosci 14:225−232

    PubMed  CAS  Google Scholar 

  • Zheng J, Trudeau MC, Zagotta WN (2002) Rod cyclic nucleotide-gated channels have a stoichiometry of three CNGA1 subunits and one CNGB1 subunit. Neuron 36:891−896

    PubMed  CAS  Google Scholar 

  • Zhong H, Molday LL, Molday RS, Yau KW (2002) The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry. Nature 420:193−198

    PubMed  CAS  Google Scholar 

  • Zhu X, Brown B, Li A, Mears AJ, Swaroop A, Craft CM (2003) GRK1-dependent phosphorylation of S and M opsins and their binding to cone arrestin during cone phototransduction in the mouse retina. J Neurosci 23:6152−6160

    PubMed  CAS  Google Scholar 

  • Zhukovsky EA, Oprian DD (1989) Effect of carboxylic acid side chains on the absorption maximum of visual pigments. Science 246:928−930

    PubMed  CAS  Google Scholar 

  • Zimmerman AL (2002) Two B or not two B? Questioning the rotational symmetry of tetrameric ion channels. Neuron 36:997−999

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C. K. Chen .

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag

About this chapter

Cite this chapter

Chen, C.K. (2005). The vertebrate phototransduction cascade: amplification and termination mechanisms. In: Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 154. Springer, Berlin, Heidelberg. https://doi.org/10.1007/s10254-005-0004-0

Download citation

Publish with us

Policies and ethics