Setting Clock Speed in Mammals: The CK1ε tau Mutation in Mice Accelerates Circadian Pacemakers by Selectively Destabilizing PERIOD Proteins

Qing Jun Meng; Larisa Logunova; Elizabeth S. Maywood; Monica Gallego; Jake Lebiecki; Timothy M. Brown; Martin Sládek; Andrei S. Semikhodskii; Nicholas R J Glossop; Hugh D. Piggins; Johanna E. Chesham; David A. Bechtold; Seung Hee Yoo; Joseph S. Takahashi; David M. Virshup; Raymond P. Boot-Handford; Michael H. Hastings; Andrew S I Loudon

doi:10.1016/j.neuron.2008.01.019

Setting Clock Speed in Mammals: The CK1ε tau Mutation in Mice Accelerates Circadian Pacemakers by Selectively Destabilizing PERIOD Proteins

Qing Jun Meng, Larisa Logunova, Elizabeth S. Maywood, Monica Gallego, Jake Lebiecki, Timothy M. Brown, Martin Sládek, Andrei S. Semikhodskii, Nicholas R J Glossop, Hugh D. Piggins, Johanna E. Chesham, David A. Bechtold, Seung Hee Yoo, Joseph S. Takahashi, David M. Virshup, Raymond P. Boot-Handford, Michael H. Hastings, Andrew S I Loudon

Research output: Contribution to journal › Article › peer-review

Abstract

The intrinsic period of circadian clocks is their defining adaptive property. To identify the biochemical mechanisms whereby casein kinase1 (CK1) determines circadian period in mammals, we created mouse null and tau mutants of Ck1 epsilon. Circadian period lengthened in CK1ε-/-, whereas CK1εtau/tau shortened circadian period of behavior in vivo and suprachiasmatic nucleus firing rates in vitro, by accelerating PERIOD-dependent molecular feedback loops. CK1εtau/tau also accelerated molecular oscillations in peripheral tissues, revealing its global role in circadian pacemaking. CK1εtau acted by promoting degradation of both nuclear and cytoplasmic PERIOD, but not CRYPTOCHROME, proteins. Together, these whole-animal and biochemical studies explain how tau, as a gain-of-function mutation, acts at a specific circadian phase to promote degradation of PERIOD proteins and thereby accelerate the mammalian clockwork in brain and periphery. © 2008 Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	78-88
Number of pages	10
Journal	Neuron
Volume	58
Issue number	1
DOIs	https://doi.org/10.1016/j.neuron.2008.01.019
Publication status	Published - 10 Apr 2008

Keywords

MOLNEURO
SYSNEURO

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10.1016/j.neuron.2008.01.019

Centre for Biological Timing
Lucas, R. (PI), Bechtold, D. (PI), Fustin, J.-M. (PI), Ashe, H. (PI), Brown, T. (PI), Blaikley, J. (PI), Brass, A. (PI), Chandola, T. (PI), Durrington, H. (PI), Else, K. (PI), Hepworth, M. (PI), Hunter, L. (PI), Kadler, K. (PI), Kitchen, G. (PI), Loudon, A. (PI), Macdonald, A. (PI), Mcbeth, J. (PI), Milosavljevic, N. (PI), Rattray, M. (PI), Rutter, M. (PI), Sharrocks, A. (PI), Spiller, D. (PI), Storchi, R. (PI), Belle, M. (PI), Meng, Q.-J. (PI), Allen, A. (PI), Dixon, W. (PI), Gibbs, J. (PI), Hazel, A. (PI), Papalopulu, N. (PI), Ray, D. (PI), White, M. (PI) & Chang, J. (PI)
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Meng, Q. J., Logunova, L., Maywood, E. S., Gallego, M., Lebiecki, J., Brown, T. M., Sládek, M., Semikhodskii, A. S., Glossop, N. R. J., Piggins, H. D., Chesham, J. E., Bechtold, D. A., Yoo, S. H., Takahashi, J. S., Virshup, D. M., Boot-Handford, R. P., Hastings, M. H., & Loudon, A. S. I. (2008). Setting Clock Speed in Mammals: The CK1ε tau Mutation in Mice Accelerates Circadian Pacemakers by Selectively Destabilizing PERIOD Proteins. Neuron, 58(1), 78-88. https://doi.org/10.1016/j.neuron.2008.01.019

@article{58c6554687f6462cb96ee150f1725a26,

title = "Setting Clock Speed in Mammals: The CK1ε tau Mutation in Mice Accelerates Circadian Pacemakers by Selectively Destabilizing PERIOD Proteins",

abstract = "The intrinsic period of circadian clocks is their defining adaptive property. To identify the biochemical mechanisms whereby casein kinase1 (CK1) determines circadian period in mammals, we created mouse null and tau mutants of Ck1 epsilon. Circadian period lengthened in CK1ε-/-, whereas CK1εtau/tau shortened circadian period of behavior in vivo and suprachiasmatic nucleus firing rates in vitro, by accelerating PERIOD-dependent molecular feedback loops. CK1εtau/tau also accelerated molecular oscillations in peripheral tissues, revealing its global role in circadian pacemaking. CK1εtau acted by promoting degradation of both nuclear and cytoplasmic PERIOD, but not CRYPTOCHROME, proteins. Together, these whole-animal and biochemical studies explain how tau, as a gain-of-function mutation, acts at a specific circadian phase to promote degradation of PERIOD proteins and thereby accelerate the mammalian clockwork in brain and periphery. {\textcopyright} 2008 Elsevier Inc. All rights reserved.",

keywords = "MOLNEURO, SYSNEURO",

author = "Meng, {Qing Jun} and Larisa Logunova and Maywood, {Elizabeth S.} and Monica Gallego and Jake Lebiecki and Brown, {Timothy M.} and Martin Sl{\'a}dek and Semikhodskii, {Andrei S.} and Glossop, {Nicholas R J} and Piggins, {Hugh D.} and Chesham, {Johanna E.} and Bechtold, {David A.} and Yoo, {Seung Hee} and Takahashi, {Joseph S.} and Virshup, {David M.} and Boot-Handford, {Raymond P.} and Hastings, {Michael H.} and Loudon, {Andrew S I}",

year = "2008",

month = apr,

day = "10",

doi = "10.1016/j.neuron.2008.01.019",

language = "English",

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Meng, QJ, Logunova, L, Maywood, ES, Gallego, M, Lebiecki, J, Brown, TM, Sládek, M, Semikhodskii, AS, Glossop, NRJ , Piggins, HD, Chesham, JE, Bechtold, DA, Yoo, SH, Takahashi, JS, Virshup, DM, Boot-Handford, RP, Hastings, MH & Loudon, ASI 2008, 'Setting Clock Speed in Mammals: The CK1ε tau Mutation in Mice Accelerates Circadian Pacemakers by Selectively Destabilizing PERIOD Proteins', Neuron, vol. 58, no. 1, pp. 78-88. https://doi.org/10.1016/j.neuron.2008.01.019

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T1 - Setting Clock Speed in Mammals: The CK1ε tau Mutation in Mice Accelerates Circadian Pacemakers by Selectively Destabilizing PERIOD Proteins

AU - Meng, Qing Jun

AU - Logunova, Larisa

AU - Maywood, Elizabeth S.

AU - Gallego, Monica

AU - Lebiecki, Jake

AU - Brown, Timothy M.

AU - Sládek, Martin

AU - Semikhodskii, Andrei S.

AU - Glossop, Nicholas R J

AU - Piggins, Hugh D.

AU - Chesham, Johanna E.

AU - Bechtold, David A.

AU - Yoo, Seung Hee

AU - Takahashi, Joseph S.

AU - Virshup, David M.

AU - Boot-Handford, Raymond P.

AU - Hastings, Michael H.

AU - Loudon, Andrew S I

PY - 2008/4/10

Y1 - 2008/4/10

N2 - The intrinsic period of circadian clocks is their defining adaptive property. To identify the biochemical mechanisms whereby casein kinase1 (CK1) determines circadian period in mammals, we created mouse null and tau mutants of Ck1 epsilon. Circadian period lengthened in CK1ε-/-, whereas CK1εtau/tau shortened circadian period of behavior in vivo and suprachiasmatic nucleus firing rates in vitro, by accelerating PERIOD-dependent molecular feedback loops. CK1εtau/tau also accelerated molecular oscillations in peripheral tissues, revealing its global role in circadian pacemaking. CK1εtau acted by promoting degradation of both nuclear and cytoplasmic PERIOD, but not CRYPTOCHROME, proteins. Together, these whole-animal and biochemical studies explain how tau, as a gain-of-function mutation, acts at a specific circadian phase to promote degradation of PERIOD proteins and thereby accelerate the mammalian clockwork in brain and periphery. © 2008 Elsevier Inc. All rights reserved.

AB - The intrinsic period of circadian clocks is their defining adaptive property. To identify the biochemical mechanisms whereby casein kinase1 (CK1) determines circadian period in mammals, we created mouse null and tau mutants of Ck1 epsilon. Circadian period lengthened in CK1ε-/-, whereas CK1εtau/tau shortened circadian period of behavior in vivo and suprachiasmatic nucleus firing rates in vitro, by accelerating PERIOD-dependent molecular feedback loops. CK1εtau/tau also accelerated molecular oscillations in peripheral tissues, revealing its global role in circadian pacemaking. CK1εtau acted by promoting degradation of both nuclear and cytoplasmic PERIOD, but not CRYPTOCHROME, proteins. Together, these whole-animal and biochemical studies explain how tau, as a gain-of-function mutation, acts at a specific circadian phase to promote degradation of PERIOD proteins and thereby accelerate the mammalian clockwork in brain and periphery. © 2008 Elsevier Inc. All rights reserved.

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KW - SYSNEURO

U2 - 10.1016/j.neuron.2008.01.019

DO - 10.1016/j.neuron.2008.01.019

M3 - Article

C2 - 18400165

SN - 0896-6273

VL - 58

SP - 78

EP - 88

JO - Neuron

JF - Neuron

IS - 1

ER -

Setting Clock Speed in Mammals: The CK1ε tau Mutation in Mice Accelerates Circadian Pacemakers by Selectively Destabilizing PERIOD Proteins

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