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Involvement of calcium/calmodulin-dependent protein kinase II in the induction of mPer1

Kazumi Nomura1, Yusuke Takeuchi, Shun Yamaguchi

  • 1Department of Pharmacology, Kumamoto University School of Medicine, Kumamoto, Japan.

Journal of Neuroscience Research
|April 15, 2003
PubMed

Insights

Calcium-calmodulin kinase II delta (CaM kinase IIdelta) activates the mPer1 gene, crucial for circadian rhythms. This kinase targets a specific DNA sequence, the 5'-GAGGGG-3' motif, to regulate mPer1 expression.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Chronobiology

Background:

  • Calcium-calmodulin kinase II (CaM kinase II) is implicated in circadian rhythm regulation.
  • The suprachiasmatic nucleus (SCN) controls light-induced circadian phase shifts.
  • mPer1 gene expression is a key component of the circadian clock.

Purpose of the Study:

  • To elucidate the intracellular mechanisms of CaM kinase II-induced mPer1 gene expression.
  • To identify the specific CaM kinase II isoform involved in mPer1 regulation.
  • To pinpoint the regulatory DNA sequence on the mPer1 promoter targeted by CaM kinase II.

Main Methods:

  • Immunoblotting and immunohistochemistry to detect CaM kinase II and IV isoforms in rat SCN.
  • Luciferase reporter gene assays to assess mPer1 promoter activity.
  • Deletion and mutation analyses of the mPer1 promoter to identify regulatory elements.

Main Results:

  • CaM kinase IIdelta was highly expressed in the rat SCN, while CaM kinase IV was not.
  • Constitutively active CaM kinase IIdelta significantly increased mPer1 promoter activity in neuronal and glioma cells.
  • A 5 extprime-GAGGGG-3 extprime sequence motif on the mPer1 promoter was identified as essential for CaM kinase II-mediated activation.

Conclusions:

  • CaM kinase IIdelta, not CaM kinase IV, plays a critical role in regulating mPer1 gene expression.
  • The 5 extprime-GAGGGG-3 extprime motif on the mPer1 promoter is a key target for CaM kinase IIdelta.
  • These findings provide insights into the molecular mechanisms of circadian gene regulation.

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