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Prolyl Isomerase Pin1 Directly Regulates Calcium/Calmodulin-Dependent Protein Kinase II Activity in Mouse Brains

Taiki Shimizu1, Kenta Kanai1, Yui Sugawara1

  • 1Molecular Enzymology, Department of Molecular Cell Science, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.

Frontiers in Pharmacology
|December 12, 2018
PubMed

Insights

Pin1 protein prevents neurodegeneration by regulating Calcium/calmodulin-dependent protein kinase II (CaMKII) activity. Pin1 binding to CaMKII reduces its activity, preserving tau phosphorylation and microtubule polymerization.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Calcium/calmodulin-dependent protein kinase II (CaMKII) is a key mediator of calcium signaling in the brain.
  • Pin1 is a peptidyl-prolyl isomerase implicated in various cellular processes.

Purpose of the Study:

  • To investigate the interaction between Pin1 and CaMKII.
  • To elucidate the role of Pin1 in regulating CaMKII activity and its downstream effects on tau phosphorylation and microtubule polymerization.

Main Methods:

  • Comparative analysis of CaMKII activity in wild-type (WT) and Pin1 knockout (Pin1-/-) mouse brains.
  • Assessment of tau phosphorylation levels.
  • Evaluation of microtubule polymerization dynamics.

Main Results:

  • CaMKII activity was significantly lower in WT mouse brains compared to Pin1-/- mouse brains.
  • Pin1 directly binds to phosphorylated CaMKII, reducing its enzymatic activity.
  • The presence of Pin1 led to lower tau phosphorylation levels and prevented CaMKII-mediated downregulation of microtubule polymerization.

Conclusions:

  • Pin1 acts as a negative regulator of CaMKII activity.
  • Pin1's interaction with CaMKII offers a novel mechanism to prevent tau hyperphosphorylation and microtubule destabilization, suggesting a potential therapeutic target for neurodegenerative diseases.
Keywords:
CaMKIIPin1prolyl isomerasetautauopathy

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