Differential roles for cryptochromes in the mammalian retinal clock

Wong Jovi C. Y.; Smyllie Nicola J.; Banks Gareth T.Pothecary Carina A.Barnard Alun R.Maywood Elizabeth S.Jagannath AartiHughes Stevenvan der Horst Gijsbertus T. J.MacLaren Robert E.Hankins Mark W.Hastings Michael H.Nolan Patrick M.Foster Russell G.Peirson Stuart N.

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Differential roles for cryptochromes in the mammalian retinal clock

机译：Differential roles for cryptochromes in the mammalian retinal clock

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Cryptochromes 1 and 2 (CRY1/2) are key components of the negative limb of the mammalian circadian clock. Like many peripheral tissues, Cry1 and -2 are expressed in the retina, where they are thought to play a role in regulating rhythmic physiology. However, studies differ in consensus as to their localization and function, and CRY1 immunostaining has not been convincingly demonstrated in the retina. Here we describe the expression and function of CRY1 and -2 in the mouse retina in both sexes. Unexpectedly, we show that CRY1 is expressed throughout all retinal layers, whereas CRY2 is restricted to the photoreceptor layer. Retinal period 2::luciferase recordings from CRY1-deficient mice show reduced clock robustness and stability, while those from CRY2-deficient mice show normal, albeit long-period, rhythms. In functional studies, we then investigated well-defined rhythms in retinal physiology. Rhythms in the photopic electroretinogram, contrast sensitivity, and pupillary light response were all severely attenuated or abolished in CRY1-deficient mice. In contrast, these physiological rhythms are largely unaffected in mice lacking CRY2, and only photopic electroretinogram rhythms are affected. Together, our data suggest that CRY1 is an essential component of the mammalian retinal clock, whereas CRY2 has a more limited role.Wong, J. C. Y., Smyllie, N. J., Banks, G. T., Pothecary, C. A., Barnard, A. R., Maywood, E. S., Jagannath, A., Hughes, S., van der Horst, G. T. J., MacLaren, R. E., Hankins, M. W., Hastings, M. H., Nolan, P. M., Foster, R. G., Peirson, S. N. Differential roles for cryptochromes in the mammalian retinal clock.

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《The FASEB Journal》 |2018年第8期|4302-4314|共13页
作者
Wong Jovi C. Y.; Smyllie Nicola J.; Banks Gareth T.Pothecary Carina A.Barnard Alun R.Maywood Elizabeth S.Jagannath AartiHughes Stevenvan der Horst Gijsbertus T. J.MacLaren Robert E.Hankins Mark W.Hastings Michael H.Nolan Patrick M.Foster Russell G.Peirson Stuart N.;
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作者单位

Univ Oxford, Sleep & Circadian Neurosci Inst, Oxford, England;

MRC, Mol Biol Lab, Cambridge, England;

MRC Harwell, Harwell Sci & Innovat Campus, Harwell, Berks, EnglandUniv Oxford, Nuffield Lab Ophthalmol, Nuffield Dept Clin Neurosci, Oxford, EnglandErasmus Univ, Dept Mol Genet, Med Ctr, Rotterdam, Netherlands;

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正文语种英语
中图分类生物化学;
关键词
circadian rhythms; retina; electroretinogram; pupillary light response; contrast sensitivity;

Differential roles for cryptochromes in the mammalian retinal clock

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