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An unusual cGMP pathway underlying depolarizing light response of the vertebrate parietal-eye photoreceptor

Nature Neuroscience volume 1, pages 359–365 (1998)Cite this article

Abstract

All cellular signaling pathways currently known to elevate cGMP involve the activation of a guanylyl cyclase to synthesize cGMP. Here we describe an exception to this rule. In the vertebrate parietal eye, the photoreceptors depolarize to light under dark-adapted conditions, unlike rods and cones but like most invertebrate photoreceptors. We report that the signaling pathway for this response involves a rise in intracellular cGMP resulting from an inhibition of the phosphodiesterase that hydrolyzes cGMP. Furthermore, this phosphodiesterase is driven by an active G protein in darkness. These results indicate an antagonistic control of the phosphodiesterase by two G proteins, analogous to the Gs/Gi control of adenylyl cyclase. Our findings demonstrate an unusual phototransduction mechanism and at the same time indicate that signaling involving cyclic nucleotides is more elaborate than previously known.

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Figure 1: Whole-cell dialysis experiments on dissociated parietal-eye photoreceptors.
Figure 2: Similarity between cGMP-induced and light-induced currents.
Figure 3: Comparison of IBMX-induced and light-induced currents.
Figure 4: Light inhibits the dark cGMP-phosphodiesterase activity in the photoreceptor.
Figure 5: A G protein is involved in the control of the cGMP-phosphodiesterase activity in darkness.
Figure 6: Possible phototransduction schemes for the parietal-eye photoreceptor.

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Acknowledgements

We thank Roger C. Hardie and Yiannis Koutalos for suggestions about experiments, and Joe Beavo, Jackie D. Corbin, Peter N. Devreotes, Vincent Manganiello, Enrico Nasi, Carol Parent, and W. Joe Thompson for discussions. Robert D. Barber, Peter G. Gillespie, Maria E. Grunwald, Dietmar Krautwurst and Haining Zhong provided comments on the manuscript. We also thank Eric Lasater for his generosity in making this collaboration possible. The L- cis -diltiazem was a gift from Tanabe Seyaku Co. (Osaka, Japan). This work was supported by a grant from the U.S. National Eye Institute.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA

    Wei-Hong Xiong & King-Wai Yau

  2. Howard Hughes Medical Institute and the Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA

    Wei-Hong Xiong & King-Wai Yau

  3. Howard Hughes Medical Institute and the Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA

    King-Wai Yau

  4. John A. Moran Eye Center, University of Utah Health Science Center, Salt Lake City, 84132, Utah, USA

    Eduardo C. Solessio

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  1. Wei-Hong Xiong
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Correspondence to King-Wai Yau.

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Xiong, WH., Solessio, E. & Yau, KW. An unusual cGMP pathway underlying depolarizing light response of the vertebrate parietal-eye photoreceptor. Nat Neurosci 1, 359–365 (1998). https://doi.org/10.1038/nn0998_359

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