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CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy

Johannes Backs1, Kunhua Song, Svetlana Bezprozvannaya

  • 1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA.

The Journal of Clinical Investigation
|June 13, 2006
PubMed

Insights

Calcium/calmodulin-dependent kinase II (CaMKII) specifically targets HDAC4, influencing its location and gene expression. This CaMKII-HDAC4 interaction is crucial for cardiac growth and calcium signaling in cells.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Epigenetics

Background:

  • Class IIa histone deacetylases (HDACs) are key regulators of cellular processes like cardiac growth and muscle development.
  • Kinase-mediated phosphorylation controls HDAC subcellular localization, but kinase-specific regulation remains unclear.

Purpose of the Study:

  • To investigate whether specific kinases selectively regulate class IIa HDACs.
  • To elucidate the signaling pathway between calcium/calmodulin-dependent kinase II (CaMKII) and HDAC4.

Main Methods:

  • Biochemical assays to identify kinase-docking sites.
  • Cellular localization studies using microscopy.
  • Analysis of gene expression changes in response to CaMKII and HDAC4 manipulation.
  • Cardiomyocyte studies to assess hypertrophic growth.

Main Results:

  • CaMKII specifically binds to HDAC4 via a unique docking site absent in other class IIa HDACs.
  • CaMKII-mediated phosphorylation of HDAC4 promotes its nuclear export and derepresses target genes.
  • CaMKII-induced HDAC4 phosphorylation drives hypertrophic growth in cardiomyocytes.

Conclusions:

  • HDAC4 is a specific target of CaMKII signaling.
  • This interaction plays a critical role in calcium-mediated control of gene expression and cardiac hypertrophy.
  • Findings have implications for understanding calcium signaling in diverse cell types.

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