Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Involvement of cyclic GMP phosphodiesterase activator in an hereditary retinal degeneration

Abstract

CYCLIC NUCLEOTIDES mediate many aspects of normal cellular metabolism1; thus, degradation as well as synthesis of these intracellular mediators must be strictly regulated. Phosphodiesterase (PDE), the enzyme of cyclic nucleotide catabolism, is present in mammalian tissues in multiple forms, which differ in substrate specificity, kinetic characteristics and sub-cellular localisation2. Moreover, a calcium-dependent protein activator (now called calmodulin) has been characterised that specifically activates at least one of the PDE types3,4 although other types of PDE are known to be activator independent5,6. Thus, several mechanisms are present in vivo which allow strict control of PDE. A unique cyclic GMP-PDE is compartmentalised in the outer segments of retinal photoreceptor cells7–10; its activity is low in the dark-adapted state but increases dramatically on light adaptation10–12. The resulting drop in cyclic GMP content could serve as a chemical ‘signal’ in the normal visual process13,14. However, despite much investigation of various cyclic nucleotide systems, no definitive information has been obtained which clearly links a disorder of cyclic nucleotide metabolism with a disease process elsewhere than in retina15,16. We have recently presented preliminary evidence that an abnormality in cyclic GMP metabolism could be present in the retinas of Irish setter dogs with inherited rod–cone dysplasia15 that could lead to greatly increased cyclic GMP content, as had been reported in mice with inherited retinal degeneration16. We now report that the basic defect in the disease seems to be a failure to switch PDE type and a concomitant decrease in protein activator concentration early in postnatal development, at the time of photoreceptor differentiation.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Robinson, G., Butcher, R. & Sutherland, E. A. Rev. Biochem. 37, 149–163 (1968).

    Article  Google Scholar 

  2. Appleman, M. & Terasaki, W. Adv. Cyclic Nucleotide Res. 5, 153–162 (1975).

    CAS  PubMed  Google Scholar 

  3. Cheung, W. Biochem. biophys. Res. Commun. 29, 478–482 (1967).

    Article  CAS  PubMed  Google Scholar 

  4. Kakiuchi, S. & Yamazaki, R. Biochem. biophys. Res. Commun. 41, 1104–1110 (1970).

    Article  CAS  PubMed  Google Scholar 

  5. Uzunov, P. & Weiss, B. Biochim. biophys. Acta 284, 220–226 (1972).

    Article  CAS  PubMed  Google Scholar 

  6. Liu, Y. & Schwartz, H. Biochim. biophys. Acta 526, 186–193 (1978).

    Article  CAS  PubMed  Google Scholar 

  7. Chader, G., Johnson, M., Fletcher, R. & Bensinger, R. J. Neurochem. 22, 93–99 (1974).

    Article  CAS  PubMed  Google Scholar 

  8. Orr, H., Lowry, O., Cohen, A. & Ferrendelli, J. Proc. natn. Acad. Sci. U.S.A. 73, 4442–4445 (1976).

    Article  ADS  CAS  Google Scholar 

  9. Farber, D. & Lolley, R. J. Neurochem. 28, 1089–1095 (1977).

    Article  CAS  PubMed  Google Scholar 

  10. Bitensky, M. et al. Adv. Cyclic Nucleotide Res. 5, 213–239 (1975).

    CAS  PubMed  Google Scholar 

  11. Chader, G., Herz, L. & Fletcher, R. Biochim. biophys. Acta 347, 491–493 (1974).

    Article  CAS  PubMed  Google Scholar 

  12. Yee, R. & Liebman, P. J. biol. Chem. 253, 8902–8909 (1978).

    CAS  PubMed  Google Scholar 

  13. Goridis, C., Virmaux, N., Cailla, H. & Delaage, M. FEBS Lett. 49, 167–169 (1974).

    Article  CAS  PubMed  Google Scholar 

  14. Fletcher, R. & Chader, G. Biochem. biophys. Res. Commun. 70, 1297–1302 (1976).

    Article  CAS  PubMed  Google Scholar 

  15. Aguirre, G., Farber, D., Lolley, R., Fletcher, R. & Chader, G. Science 201, 1133–1134 (1978).

    Article  ADS  CAS  Google Scholar 

  16. Farber, D. & Lolley, R. Science 186, 449–451 (1974).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Lowry, O., Rosebrough, N., Farr, A. & Randall, R. J. biol. Chem. 193, 265–275 (1951).

    CAS  PubMed  Google Scholar 

  18. Lin, Y., Liu, Y. & Cheung, W. J. biol. Chem. 249, 4943–4954 (1974).

    CAS  PubMed  Google Scholar 

  19. Hebel, R. Adv. Anat. Embryol. Cell Biol. 45, 1–92 (1971).

    Google Scholar 

  20. Teo, T. & Wang, J. J. biol. Chem. 248, 5950–5955 (1973).

    CAS  PubMed  Google Scholar 

  21. Liu, Y. & Cheung, W. J. biol. Chem. 251, 4193–4198 (1976).

    CAS  PubMed  Google Scholar 

  22. Kakiuchi, S., Yamazaki, R., Teshima, Y. & Uenishi, K. Proc. natn. Acad. Sci. U.S.A. 70, 3526–3531 (1973).

    Article  ADS  CAS  Google Scholar 

  23. Villee, C. Fedn Proc. 25, 874–878 (1966).

    CAS  Google Scholar 

  24. Greengard, O. & Thorndike, J. Enzyme 17, 333–378 (1974).

    Article  CAS  PubMed  Google Scholar 

  25. Tanigawa, Y., Shimoyama, M., Tai, J., Fujii, K. & Veda, I. Biochem. biophys. Res. Commun. 73, 19–24 (1976).

    Article  CAS  PubMed  Google Scholar 

  26. Singer, A., Dunn, A. & Appleman, M. Archs Biochem. Biophys. 187, 406–413 (1978).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

LIU, Y., KRISHNA, G., AGUIRRE, G. et al. Involvement of cyclic GMP phosphodiesterase activator in an hereditary retinal degeneration. Nature 280, 62–64 (1979). https://doi.org/10.1038/280062a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/280062a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing