TY - JOUR
T1 - Physiological and pathological roles of CaMKII-PP1 signaling in the brain
AU - Shioda, Norifumi
AU - Fukunaga, Kohji
N1 - Funding Information:
Acknowledgments: This work was supported by MEXT/JSPS KAKENHI Grant 25460090 (to Norifumi Shioda). Author Contributions: Norifumi Shioda and Kohji Fukunaga wrote the manuscript. Conflicts of Interest: The authors declare no conflict of interest.
Funding Information:
This work was supported by MEXT/JSPS KAKENHI Grant 25460090 (to Norifumi Shioda).
Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/1
Y1 - 2018/1
N2 - 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.
AB - 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.
KW - Ca/calmodulin-dependent protein kinase II
KW - Nuclear translocation
KW - Protein phosphatase-1
KW - Synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=85039757225&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85039757225&partnerID=8YFLogxK
U2 - 10.3390/ijms19010020
DO - 10.3390/ijms19010020
M3 - Review article
C2 - 29271887
AN - SCOPUS:85039757225
VL - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 1
M1 - 20
ER -