Cited by 41Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchProtein Kinase Regulation and GTPase Signaling

Regulation of CaMKII by α4/PP2Ac contributes to learning and memory

Yamashita, Takeshi, Inui, Seiji, Maeda, Kazuhiko, Hua, Ding Rong, Takagi, Katsumasa, Fukunaga, Kohji, Sakaguchi, Nobuo·2006·Brain Research

Abstract

Ca(2+)-dependent CaMKIIalpha activation with autophosphorylation plays an essential role in learning and memory. The regulation of CaMKIIalpha by dephosphorylation by protein phosphatase 1 (PP1) has been demonstrated. We addressed whether the protein phosphatase 2A (PP2A) that is abundant in the brain could be involved in the regulation of CaMKIIalpha. CaMKIIalpha was associated with the catalytic subunit of PP2A (PP2Ac) and alpha4, a regulator of PP2A. To investigate whether alpha4 plays an important role in the CNS, we established a neuron specific Cre transgenic mouse and a neuron specific alpha4 deficient mouse (N-alpha4 KO mouse). This N-alpha4 KO mouse showed impaired learning and memory in a water maze and also shuttle-box avoidance test. The activity of CaMKIIalpha also increased in hippocampus. An overexpression of alpha4 in the neuronal cell line demonstrated the activity of CaMKIIalpha to be regulated by alpha4. alpha4 and PP2Ac were localized in the cytoplasm but not in the postsynaptic density (PSD), thus suggesting that the dephosphorylation of CaMKIIalpha by alpha4/PP2Ac occurred in the cytoplasm. These results suggest that alpha4 and PP2A may thus play an important role in CaMKIIalpha regulation and thereby also influence learning.

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Crossref · 10.1016/j.brainres.2006.01.101

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  • Brain-specific α4 knockout mice showed impaired learning and memory (measured through spatial learning and shuttle box avoidance tests), but no sensorimotor or motivational deficiencies.

    “Nevertheless, the brain-specific α4 KO mice did show impaired learning and memory (measured through spatial learning and shuttle box avoidance tests), but no sensorimotor or motivational deficiencies.”
  • Conditional knockout of α4 in neurons did not result in any gross abnormalities in brain development, despite clearly decreased overall PP2A activity in hippocampal extracts.

    “In contrast, conditional KO of α4 in neurons did not result in any gross abnormalities in brain development, despite clearly decreased overall PP2A activity in hippocampal extracts [48].”
  • The presumed dysfunction of the hippocampus correlated with increased activity of CaMKIIα.

    “The presumed dysfunction of the hippocampus correlated with increased activity of CaMKIIα [48].”

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Authors
Yamashita, T., Inui, S., Maeda, K., Hua, D. R., Takagi, K., Fukunaga, K., & Sakaguchi, N.
Affiliations
  • Kumamoto University (JP)
  • Tohoku University (JP)
  • Japan Science and Technology Agency (JP)
Corresponding author
Sakaguchi, Nobuo
Venue
Brain Research
Publisher
Elsevier BV
Published
2006-04
Volume
1082
Issue
1
Pages
1-10
ISSN
0006-8993 (ISSN-L)
OpenAlex
W2046287986
Cited by
41
References
29
Citations by year
2023: 2 · 2022: 2 · 2021: 5 · 2019: 3 · 2018: 3 · 2016: 1 · 2015: 1 · 2014: 5 · 2013: 2 · 2012: 4
FWCI
1.29
Type
journal article
Language
en
Open access
closed
Locations
  • Brain Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
CaMKIIα, protein phosphatase 2A, PP2A catalytic subunit, dephosphorylation, autophosphorylation, learning and memory, hippocampus, postsynaptic density
MeSH terms
Analysis of Variance, Animals, Avoidance Learning, Behavior, Animal, Brain, Enzyme Activation, Gene Expression Regulation, Learning, Mice, Inbred C57BL, Neuroblastoma, Phosphoprotein Phosphatases, Phosphoproteins, Reaction Time, Transfection, Blotting, Western, Calcium-Calmodulin-Dependent Protein Kinases, Mice, Knockout, Maze Learning, Molecular Chaperones, Intercellular Signaling Peptides and Proteins, Cell Line, Tumor, Immunoprecipitation, Adaptor Proteins, Signal Transducing, Mice, Protein Phosphatase 1, Protein Phosphatase 2, Calcium-Calmodulin-Dependent Protein Kinase Type 2

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