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Peptidyl-prolyl Isomerases in Human Pathologies

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Front. Pharmacol. | doi: 10.3389/fphar.2018.01351

Prolyl isomerase Pin1 directly regulates calcium/calmodulin-dependent protein kinase II activity in mouse brains

 Taiki Shimizu1, Kenta Kanai1, Yui Sugawara1, Chiyoko Uchida2 and  Takafumi Uchida1*
  • 1Tohoku University, Japan
  • 2Fukushima University, Japan

Calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the brain and functions as a mediator of calcium signaling. We found that the relative activity of CaMKII was significantly lower in the WT mouse brains than in the Pin1-/- mouse brains. Pin1 binds to phosphorylated CaMKII and weakens its activity. For this reason, the phosphorylation level of tau in the presence of Pin1 is lower than that in the absence of Pin1, and microtubule polymerization is not downregulated by CaMKII when Pin1 is present. These results suggest a novel mechanism of action of Pin1 to prevent neurodegeneration.

Keywords: Prolyl isomerase, Pin1, CaMKII, tau, Tauopathy

Received: 06 Sep 2018; Accepted: 05 Nov 2018.

Edited by:

Tiziano Tuccinardi, University of Pisa, Italy

Reviewed by:

Isabelle Landrieu, UMR8576 Unité de glycobiologie structurale et fonctionnelle, France
Cordelia Schiene-Fischer, Martin Luther University of Halle-Wittenberg, Germany  

Copyright: © 2018 Shimizu, Kanai, Sugawara, Uchida and Uchida. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Takafumi Uchida, Tohoku University, Aoba-ku, Sendai, 980-8577, Miyagi, Japan, uchidataka@gmail.com