Next Article in Journal
Modulatory Effects of Breed, Feeding Status, and Diet on Adipogenic, Lipogenic, and Lipolytic Gene Expression in Growing Iberian and Duroc Pigs
Next Article in Special Issue
The Influence of EGFR Inactivation on the Radiation Response in High Grade Glioma
Previous Article in Journal
Assessing the Effectiveness of a Far-Red Fluorescent Reporter for Tracking Stem Cells In Vivo
Previous Article in Special Issue
Protein Kinase Targets in Breast Cancer
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2018, 19(1), 20; https://doi.org/10.3390/ijms19010020

Physiological and Pathological Roles of CaMKII-PP1 Signaling in the Brain

1
Department of Biofunctional Analysis Laboratory of Molecular Biology, Gifu Pharmaceutical University, 1-25-4 daigaku-nishi, Gifu 501-1196, Japan
2
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai, Miyagi 980-8578, Japan
*
Authors to whom correspondence should be addressed.
Received: 23 November 2017 / Revised: 19 December 2017 / Accepted: 20 December 2017 / Published: 22 December 2017
(This article belongs to the Special Issue Kinase Signal Transduction 2017)
Full-Text   |   PDF [669 KB, uploaded 22 December 2017]   |  

Abstract

Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII), a multifunctional serine (Ser)/threonine (Thr) protein kinase, regulates diverse activities related to Ca2+-mediated neuronal plasticity in the brain, including synaptic activity and gene expression. Among its regulators, protein phosphatase-1 (PP1), a Ser/Thr phosphatase, appears to be critical in controlling CaMKII-dependent neuronal signaling. In postsynaptic densities (PSDs), CaMKII is required for hippocampal long-term potentiation (LTP), a cellular process correlated with learning and memory. In response to Ca2+ elevation during hippocampal LTP induction, CaMKIIα, an isoform that translocates from the cytosol to PSDs, is activated through autophosphorylation at Thr286, generating autonomous kinase activity and a prolonged Ca2+/CaM-bound state. Moreover, PP1 inhibition enhances Thr286 autophosphorylation of CaMKIIα during LTP induction. By contrast, CaMKII nuclear import is regulated by Ser332 phosphorylation state. CaMKIIδ3, a nuclear isoform, is dephosphorylated at Ser332 by PP1, promoting its nuclear translocation, where it regulates transcription. In this review, we summarize physio-pathological roles of CaMKII/PP1 signaling in neurons. CaMKII and PP1 crosstalk and regulation of gene expression is important for neuronal plasticity as well as survival and/or differentiation. View Full-Text
Keywords: Ca2+/calmodulin-dependent protein kinase II; protein phosphatase-1; synaptic plasticity; nuclear translocation Ca2+/calmodulin-dependent protein kinase II; protein phosphatase-1; synaptic plasticity; nuclear translocation
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Shioda, N.; Fukunaga, K. Physiological and Pathological Roles of CaMKII-PP1 Signaling in the Brain. Int. J. Mol. Sci. 2018, 19, 20.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top