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| 题名: | Calcineurin serves in the circadian output pathway to regulate the daily rhythm of l-type voltage-gated calcium channels in the retina |
| 作者: | 黃佳瑜;Huang, Cathy Chia-Yu;Ko, Michael L.;Vernikovskaya, Darya I.;Ko, Gladys Y.-P. |
| 贡献者: | 生醫理工學院生命科學系 |
| 关键词: | Animals;CALCINEURIN;Calcineurin - metabolism;CALCIUM CHANNEL;Calcium Channels, L-Type - metabolism;Chick Embryo;CIRCADIAN RHYTHM;Extracellular Signal-Regulated MAP Kinases - metabolism;Phosphatidylinositol 3-Kinases - metabolism;Proto-Oncogene Proteins c-akt - metabolism;Retina - enzymology;Retina - physiology;Signal Transduction;SIGNALING |
| 日期: | 2012-03-01 |
| 上传时间: | 2026-04-23 11:11:54 (UTC+8) |
| 出版者: | Wiley-Liss Inc.;Hoboken: Wiley Subscription Services, Inc., A Wiley Company |
| 摘要: | 摘要： AbstractThe L‐type voltage‐gated calcium channels (L‐VGCCs) in avian retinal cone photoreceptors are under circadian control, in which the protein expression of the α1 subunits and the current density are greater at night than during the day. Both Ras‐mitogen‐activated protein kinase (MAPK) and Ras‐phosphatidylionositol 3 kinase‐protein kinase B (PI3K‐AKT) signaling pathways are part of the circadian output that regulate the L‐VGCC rhythm, while cAMP‐dependent signaling is further upstream of Ras to regulate the circadian outputs in photoreceptors. However, there are missing links between cAMP‐dependent signaling and Ras in the circadian output regulation of L‐VGCCs. In this study, we report that calcineurin, a Ca2+/calmodulin‐dependent serine (ser)/threonine (thr) phosphatase, participates in the circadian output pathway to regulate L‐VGCCs through modulating both Ras‐MAPK and Ras‐PI3K‐AKT signaling. The activity of calcineurin, but not its protein expression, was under circadian regulation. Application of a calcineurin inhibitor, FK‐506 or cyclosporine A, reduced the L‐VGCC current density at night with a corresponding decrease in L‐VGCCα1D protein expression, but the circadian rhythm of L‐VGCCα1D mRNA levels were not affected. Inhibition of calcineurin further reduced the phosphorylation of ERK and AKT (at thr 308) and inhibited the activation of Ras, but inhibitors of MAPK or PI3K signaling did not affect the circadian rhythm of calcineurin activity. However, inhibition of adenylate cyclase significantly dampened the circadian rhythm of calcineurin activity. These results suggest that calcineurin is upstream of MAPK and PI3K‐AKT but downstream of cAMP in the circadian regulation of L‐VGCCs. J. Cell. Biochem. 113: 911–922, 2012. © 2011 Wiley Periodicals, Inc.
其他題名： J. Cell. Biochem
出版者： Hoboken: Wiley Subscription Services, Inc., A Wiley Company
出版日期： 2012-03
出處： Journal of Cellular Biochemistry, 2012-03, Vol.113 (3), p.911-922
資源來源： Wiley Online Library
版權： Copyright © 2011 Wiley Periodicals, Inc.
版權： 2011 Wiley Periodicals, Inc.
識別號： ISSN: 0730-2312
識別號： ISSN: 1097-4644
識別號： EISSN: 1097-4644
識別號： DOI: 10.1002/jcb.23419
識別號： PMID: 22371971 |
| 显示于类别: | [生命科學系] 期刊論文
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