Physiological and Pathological Roles of CaMKII-PP1 Signaling in the Brain
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 phosphatas...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2017-12-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/19/1/20 |
id |
doaj-0392e6c9dc7a483aaebddb6f346cf9e7 |
---|---|
record_format |
Article |
spelling |
doaj-0392e6c9dc7a483aaebddb6f346cf9e72020-11-25T01:30:37ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-12-011912010.3390/ijms19010020ijms19010020Physiological and Pathological Roles of CaMKII-PP1 Signaling in the BrainNorifumi Shioda0Kohji Fukunaga1Department of Biofunctional Analysis Laboratory of Molecular Biology, Gifu Pharmaceutical University, 1-25-4 daigaku-nishi, Gifu 501-1196, JapanDepartment of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai, Miyagi 980-8578, JapanCa2+/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.https://www.mdpi.com/1422-0067/19/1/20Ca2+/calmodulin-dependent protein kinase IIprotein phosphatase-1synaptic plasticitynuclear translocation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Norifumi Shioda Kohji Fukunaga |
spellingShingle |
Norifumi Shioda Kohji Fukunaga Physiological and Pathological Roles of CaMKII-PP1 Signaling in the Brain International Journal of Molecular Sciences Ca2+/calmodulin-dependent protein kinase II protein phosphatase-1 synaptic plasticity nuclear translocation |
author_facet |
Norifumi Shioda Kohji Fukunaga |
author_sort |
Norifumi Shioda |
title |
Physiological and Pathological Roles of CaMKII-PP1 Signaling in the Brain |
title_short |
Physiological and Pathological Roles of CaMKII-PP1 Signaling in the Brain |
title_full |
Physiological and Pathological Roles of CaMKII-PP1 Signaling in the Brain |
title_fullStr |
Physiological and Pathological Roles of CaMKII-PP1 Signaling in the Brain |
title_full_unstemmed |
Physiological and Pathological Roles of CaMKII-PP1 Signaling in the Brain |
title_sort |
physiological and pathological roles of camkii-pp1 signaling in the brain |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2017-12-01 |
description |
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. |
topic |
Ca2+/calmodulin-dependent protein kinase II protein phosphatase-1 synaptic plasticity nuclear translocation |
url |
https://www.mdpi.com/1422-0067/19/1/20 |
work_keys_str_mv |
AT norifumishioda physiologicalandpathologicalrolesofcamkiipp1signalinginthebrain AT kohjifukunaga physiologicalandpathologicalrolesofcamkiipp1signalinginthebrain |
_version_ |
1725091128608292864 |