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. 2000 Dec;79(6):2801–2817. doi: 10.1016/S0006-3495(00)76519-2

Engineering aspects of enzymatic signal transduction: photoreceptors in the retina.

P B Detwiler 1, S Ramanathan 1, A Sengupta 1, B I Shraiman 1
PMCID: PMC1301161  PMID: 11106590

Abstract

Identifying the basic module of enzymatic amplification as an irreversible cycle of messenger activation/deactivation by a "push-pull" pair of opposing enzymes, we analyze it in terms of gain, bandwidth, noise, and power consumption. The enzymatic signal transduction cascade is viewed as an information channel, the design of which is governed by the statistical properties of the input and the noise and dynamic range constraints of the output. With the example of vertebrate phototransduction cascade we demonstrate that all of the relevant engineering parameters are controlled by enzyme concentrations and, from functional considerations, derive bounds on the required protein numbers. Conversely, the ability of enzymatic networks to change their response characteristics by varying only the abundance of different enzymes illustrates how functional diversity may be built from nearly conserved molecular components.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alon U., Surette M. G., Barkai N., Leibler S. Robustness in bacterial chemotaxis. Nature. 1999 Jan 14;397(6715):168–171. doi: 10.1038/16483. [DOI] [PubMed] [Google Scholar]
  2. Barkai N., Leibler S. Robustness in simple biochemical networks. Nature. 1997 Jun 26;387(6636):913–917. doi: 10.1038/43199. [DOI] [PubMed] [Google Scholar]
  3. Baylor D. A., Hodgkin A. L., Lamb T. D. The electrical response of turtle cones to flashes and steps of light. J Physiol. 1974 Nov;242(3):685–727. doi: 10.1113/jphysiol.1974.sp010731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baylor D. How photons start vision. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):560–565. doi: 10.1073/pnas.93.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berg H. C. Bacterial microprocessing. Cold Spring Harb Symp Quant Biol. 1990;55:539–545. doi: 10.1101/sqb.1990.055.01.052. [DOI] [PubMed] [Google Scholar]
  6. Bodoia R. D., Detwiler P. B. Patch-clamp recordings of the light-sensitive dark noise in retinal rods from the lizard and frog. J Physiol. 1985 Oct;367:183–216. doi: 10.1113/jphysiol.1985.sp015820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bray D. Protein molecules as computational elements in living cells. Nature. 1995 Jul 27;376(6538):307–312. doi: 10.1038/376307a0. [DOI] [PubMed] [Google Scholar]
  8. Chen C. K., Burns M. E., He W., Wensel T. G., Baylor D. A., Simon M. I. Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1. Nature. 2000 Feb 3;403(6769):557–560. doi: 10.1038/35000601. [DOI] [PubMed] [Google Scholar]
  9. Chock P. B., Stadtman E. R. Superiority of interconvertible enzyme cascades in metabolite regulation: analysis of multicyclic systems. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2766–2770. doi: 10.1073/pnas.74.7.2766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fawzi A. B., Northup J. K. Guanine nucleotide binding characteristics of transducin: essential role of rhodopsin for rapid exchange of guanine nucleotides. Biochemistry. 1990 Apr 17;29(15):3804–3812. doi: 10.1021/bi00467a030. [DOI] [PubMed] [Google Scholar]
  11. Gold G. H., Pugh E. N., Jr Olfactory adaptation. The nose leads the eye. Nature. 1997 Feb 20;385(6618):677–679. doi: 10.1038/385677a0. [DOI] [PubMed] [Google Scholar]
  12. Gorczyca W. A., Gray-Keller M. P., Detwiler P. B., Palczewski K. Purification and physiological evaluation of a guanylate cyclase activating protein from retinal rods. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4014–4018. doi: 10.1073/pnas.91.9.4014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gray-Keller M. P., Detwiler P. B. The calcium feedback signal in the phototransduction cascade of vertebrate rods. Neuron. 1994 Oct;13(4):849–861. doi: 10.1016/0896-6273(94)90251-8. [DOI] [PubMed] [Google Scholar]
  14. Gray-Keller M., Denk W., Shraiman B., Detwiler P. B. Longitudinal spread of second messenger signals in isolated rod outer segments of lizards. J Physiol. 1999 Sep 15;519(Pt 3):679–692. doi: 10.1111/j.1469-7793.1999.0679n.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. He W., Cowan C. W., Wensel T. G. RGS9, a GTPase accelerator for phototransduction. Neuron. 1998 Jan;20(1):95–102. doi: 10.1016/s0896-6273(00)80437-7. [DOI] [PubMed] [Google Scholar]
  16. Klenchin V. A., Calvert P. D., Bownds M. D. Inhibition of rhodopsin kinase by recoverin. Further evidence for a negative feedback system in phototransduction. J Biol Chem. 1995 Jul 7;270(27):16147–16152. doi: 10.1074/jbc.270.27.16147. [DOI] [PubMed] [Google Scholar]
  17. Koch K. W., Stryer L. Highly cooperative feedback control of retinal rod guanylate cyclase by calcium ions. Nature. 1988 Jul 7;334(6177):64–66. doi: 10.1038/334064a0. [DOI] [PubMed] [Google Scholar]
  18. Kolesnikov S. S., Margolskee R. F. A cyclic-nucleotide-suppressible conductance activated by transducin in taste cells. Nature. 1995 Jul 6;376(6535):85–88. doi: 10.1038/376085a0. [DOI] [PubMed] [Google Scholar]
  19. Koshland D. E., Jr, Goldbeter A., Stock J. B. Amplification and adaptation in regulatory and sensory systems. Science. 1982 Jul 16;217(4556):220–225. doi: 10.1126/science.7089556. [DOI] [PubMed] [Google Scholar]
  20. Koutalos Y., Yau K. W. Regulation of sensitivity in vertebrate rod photoreceptors by calcium. Trends Neurosci. 1996 Feb;19(2):73–81. doi: 10.1016/0166-2236(96)89624-x. [DOI] [PubMed] [Google Scholar]
  21. Lamb T. D., Pugh E. N., Jr A quantitative account of the activation steps involved in phototransduction in amphibian photoreceptors. J Physiol. 1992 Apr;449:719–758. doi: 10.1113/jphysiol.1992.sp019111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Laughlin S. A simple coding procedure enhances a neuron's information capacity. Z Naturforsch C. 1981 Sep-Oct;36(9-10):910–912. [PubMed] [Google Scholar]
  23. Naka K. I., Itoh M. A., Chappell R. L. Dynamics of turtle cones. J Gen Physiol. 1987 Feb;89(2):321–337. doi: 10.1085/jgp.89.2.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nikonov S., Engheta N., Pugh E. N., Jr Kinetics of recovery of the dark-adapted salamander rod photoresponse. J Gen Physiol. 1998 Jan;111(1):7–37. doi: 10.1085/jgp.111.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Normann R. A., Perlman I. The effects of background illumination on the photoresponses of red and green cones. J Physiol. 1979 Jan;286:491–507. doi: 10.1113/jphysiol.1979.sp012633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pepperberg D. R., Cornwall M. C., Kahlert M., Hofmann K. P., Jin J., Jones G. J., Ripps H. Light-dependent delay in the falling phase of the retinal rod photoresponse. Vis Neurosci. 1992 Jan;8(1):9–18. doi: 10.1017/s0952523800006441. [DOI] [PubMed] [Google Scholar]
  27. Reed R. R. How does the nose know? Cell. 1990 Jan 12;60(1):1–2. doi: 10.1016/0092-8674(90)90706-k. [DOI] [PubMed] [Google Scholar]
  28. Rieke F., Baylor D. A. Molecular origin of continuous dark noise in rod photoreceptors. Biophys J. 1996 Nov;71(5):2553–2572. doi: 10.1016/S0006-3495(96)79448-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rieke F., Baylor D. A. Origin of reproducibility in the responses of retinal rods to single photons. Biophys J. 1998 Oct;75(4):1836–1857. doi: 10.1016/S0006-3495(98)77625-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rieke F., Schwartz E. A. A cGMP-gated current can control exocytosis at cone synapses. Neuron. 1994 Oct;13(4):863–873. doi: 10.1016/0896-6273(94)90252-6. [DOI] [PubMed] [Google Scholar]
  31. Rispoli G., Sather W. A., Detwiler P. B. Visual transduction in dialysed detached rod outer segments from lizard retina. J Physiol. 1993 Jun;465:513–537. doi: 10.1113/jphysiol.1993.sp019691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Simon M. I., Strathmann M. P., Gautam N. Diversity of G proteins in signal transduction. Science. 1991 May 10;252(5007):802–808. doi: 10.1126/science.1902986. [DOI] [PubMed] [Google Scholar]
  33. Stadtman E. R., Chock P. B. Superiority of interconvertible enzyme cascades in metabolic regulation: analysis of monocyclic systems. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2761–2765. doi: 10.1073/pnas.74.7.2761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stryer L. Visual excitation and recovery. J Biol Chem. 1991 Jun 15;266(17):10711–10714. [PubMed] [Google Scholar]
  35. Tranchina D., Sneyd J., Cadenas I. D. Light adaptation in turtle cones. Testing and analysis of a model for phototransduction. Biophys J. 1991 Jul;60(1):217–237. doi: 10.1016/S0006-3495(91)82045-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Turrigiano G., Abbott L. F., Marder E. Activity-dependent changes in the intrinsic properties of cultured neurons. Science. 1994 May 13;264(5161):974–977. doi: 10.1126/science.8178157. [DOI] [PubMed] [Google Scholar]
  37. Wray G. A. Promoter logic. Science. 1998 Mar 20;279(5358):1871–1872. doi: 10.1126/science.279.5358.1871. [DOI] [PubMed] [Google Scholar]

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