Regulation of CaMKII by alpha4/PP2Ac contributes to learning and memory

Brain Research
Takeshi YamashitaNobuo Sakaguchi

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...Continue Reading

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Citations

Nov 4, 2010·Neurochemical Research·Abdur RahmanGilles J Guillemin
Sep 21, 2010·Biochemical and Biophysical Research Communications·Ryutaro KajiharaSeiji Inui
Jan 22, 2009·Molecular Systems Biology·Timo GlatterMatthias Gstaiger
Jun 23, 2010·Journal of Neuroscience Research·Miguel A R AmorimLuis M Garcia-Segura
Jun 5, 2019·Proceedings of the National Academy of Sciences of the United States of America·Jie WangZhi-Qi Xiong
May 6, 2009·Neurochemical Research·Kathryn A Skelding, John A P Rostas
Mar 21, 2018·Molecular and Cellular Biology·Hee Kyoung ChungJian-Ying Wang
Jul 3, 2021·Cancers·Jean-Paul BryantYeshavanth Kumar Banasavadi-Siddegowda
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Jul 1, 2008·Biochimica Et Biophysica Acta·Pieter J A EichhornRené Bernards

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