Abstract
The type A GABA receptors are thought to mediate synchronization of clock cell activity within the suprachiasmatic nuclei (SCN). Here we report that casein kinases I ε and δ (CKIε and CKIδ), the crucial clock regulators, form a complex with GABAA receptors and inhibit the receptors' function within the SCN according to a circadian rhythm. These results indicate that circadian variation of the kinase-receptor association may mediate regulation of GABAA receptor function by CKIε-CKIδ in the SCN.
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Acknowledgements
This work was supported by a grant to Q.W. from Canadian Institutes of Health Research (CIHR). Q.W. is a CIHR New Investigator.
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Supplementary information
Supplementary Fig. 1
Rhythmic variation of the physical association between GABAARs and CKIε/δ in the SCN. (a,b) Immunoprecipitation performed with an anti-GABAAR β2/3 antibody led to the coprecipitation of CKIε (a) or CKIδ (b) at the early light phase (ZT2-4) of LD cycle, but at ZT14-16 of the early dark phase, remarkably fewer CKIε (a) or CKIδ (b) were coprecipitated by anti-GABAAR β2/3 from the SCN tissues. Graphs on the right panels summarize the rhythmic variation of the kinase-receptor complexes (Student's t-test, *P < 0.05). Data shown in each graph are normalized to the average measured in control and are means ± s.d. of four determinations. (JPG 39 kb)
Supplementary Fig. 2
pecificity of GABAAR-CKIε interactions in the SCN. (a) The anti-CKIε antibody coprecipitates the same amount of GABAAR β2/3 subunits in rat hippocampal CA1 tissues at both ZT2-4 and ZT14-16 in LD, suggesting that the rhythmic variation of GABAAR-CKIε association is specific to the SCN. Data shown in the graph are normalized to the average measured in control and are means ± s.d. of four determinations (Student's t-test, P > 0.05). (b) The anti-CKIε antibody coprecipitated GABAAR β2/3, but not NMDA receptor NR1 subunits in the SCN tissues at ZT2-4 in LD cycle, indicating a specific regulation of GABAARs by CKIε in the SCN. (JPG 31 kb)
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Ning, K., Li, L., Liao, M. et al. Circadian regulation of GABAA receptor function by CKIε-CKIδ in the rat suprachiasmatic nuclei. Nat Neurosci 7, 489–490 (2004). https://doi.org/10.1038/nn1236
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DOI: https://doi.org/10.1038/nn1236
