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Prolonged photoresponses in transgenic mouse rods lacking arrestin

Nature volume 389, pages 505–509 (1997)Cite this article

Abstract

Arrestins are soluble cytoplasmic proteins that bind to G-protein-coupled receptors, thus switching off activation of the G protein and terminating the signalling pathway that triggers the cellular response1,2. Although visual arrestin has been shown to quench the catalytic activity of photoexcited, phosphorylated rhodopsin in a reconstituted system3, its role in the intact rod cell remains unclear because phosphorylation alone reduces the catalytic activity of rhodopsin4,5,6. Here we have recorded photocurrents of rods from transgenic mice in which one or both copies of the arrestin gene were disrupted. Photoresponses were unaffected when arrestin expression was halved, indicating that arrestin binding is not rate limiting for recovery of the rod photoresponse, as it is in Drosophila7,8. With arrestin absent, the flash response displayed a rapid partial recovery followed by a prolonged final phase. This behaviour indicates that an arrestin-independent mechanism initiates the quench of rhodopsin's catalytic activity and that arrestin completes the quench. The intensity dependence of the photoresponse in rods lacking arrestin further suggests that, although arrestin is required for normal signal termination, it does not participate directly in light adaptation.

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Figure 1: Targeted disruption of rod arrestin.
Figure 2: Targeted disruption of rod arrestin.
Figure 3: Morphology of the central retina of cyclic-light-reared control and arrestin knockout mice at 4 weeks of age.
Figure 4: Rod flash responses.
Figure 5: Rod flash responses.
Figure 6: Rod flash responses.
Figure 7: Rod flash responses.
Figure 8: Rod flash responses.
Figure 9: Lack of arrestin leaves the mechanism of light adaptation intact.
Figure 10: Lack of arrestin leaves the mechanism of light adaptation intact.

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Acknowledgements

This work was supported by grants from the National Eye Institute (D.A.B.), the National Institute on Aging (M.I.S.), the National Institute of General Medical Sciences (R.L.D.), the Ruth and Milton Steinbach Fund (D.A.B., J.C.), The McKnight Endowment Fund for Neuroscience (D.A.B.), Research to Prevent Blindness (J.C., C.L.M.) and Lions' of Massachusetts (C.L.M.).

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Author notes

  1. Jun Xu

    Present address: Cadus Pharmaceutical Corporation, 777 Old Saw Mill River Road, Tarrytown, New York, 10591, USA

  2. Clint L. Makino

    Present address: Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, 02114, USA

  3. Jeannie Chen

    Present address: Mary D. Allen Laboratory for Vision Research, Doheny Eye Institute, Departments of Ophthalmology and Cell and Neurobiology, University of Southern California School of Medicine, Los Angeles, California, 90033, USA

  4. Jun Xu and Robert L. Dodd: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Biology, California Institute of Technology, Pasadena, 91125, California, USA

    Jun Xu, Melvin I. Simon & Jeannie Chen

  2. Department of Neurobiology, Stanford University School of Medicine, Stanford, 94305, California, USA

    Robert L. Dodd, Clint L. Makino & Denis A. Baylor

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  1. Jun Xu
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Correspondence to Denis A. Baylor.

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Xu, J., Dodd, R., Makino, C. et al. Prolonged photoresponses in transgenic mouse rods lacking arrestin. Nature 389, 505–509 (1997). https://doi.org/10.1038/39068

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