Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ

Hiroyuki Okuno, Kaori Akashi, Yuichiro Ishii, Nan Yagishita-Kyo, Kanzo Suzuki, Mio Nonaka, Takashi Kawashima, Hajime Fujii, Sayaka Takemoto-Kimura, Manabu Abe, Rie Natsume, Shoaib Chowdhury, Kenji Sakimura, Paul F Worley, Haruhiko Bito

Research output: Contribution to journalArticle

Abstract

The Arc/Arg3.1 gene product is rapidly upregulated by strong synaptic activity and critically contributes to weakening synapses by promoting AMPA-R endocytosis. However, how activity-induced Arc is redistributed and determines the synapses to be weakened remains unclear. Here, we show targeting of Arc to inactive synapses via a high-affinity interaction with CaMKIIβ that is not bound to calmodulin. Synaptic Arc accumulates in inactive synapses that previously experienced strong activation and correlates with removal of surface GluA1 from individual synapses. A lack of CaMKIIβ either in vitro or in vivo resulted in loss of Arc upregulation in the silenced synapses. The discovery of Arc's role in "inverse" synaptic tagging that is specific for weaker synapses and prevents undesired enhancement of weak synapses in potentiated neurons reconciles essential roles of Arc both for the late phase of long-term plasticity and for reduction of surface AMPA-Rs in stimulated neurons.

Original languageEnglish (US)
Pages (from-to)886-898
Number of pages13
JournalCell
Volume149
Issue number4
DOIs
StatePublished - May 11 2012

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Calcium-Calmodulin-Dependent Protein Kinase Type 2
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Synapses
Neurons
Calmodulin
Plasticity
Genes
Chemical activation
Endocytosis
Up-Regulation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Okuno, H., Akashi, K., Ishii, Y., Yagishita-Kyo, N., Suzuki, K., Nonaka, M., ... Bito, H. (2012). Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ. Cell, 149(4), 886-898. https://doi.org/10.1016/j.cell.2012.02.062

Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ. / Okuno, Hiroyuki; Akashi, Kaori; Ishii, Yuichiro; Yagishita-Kyo, Nan; Suzuki, Kanzo; Nonaka, Mio; Kawashima, Takashi; Fujii, Hajime; Takemoto-Kimura, Sayaka; Abe, Manabu; Natsume, Rie; Chowdhury, Shoaib; Sakimura, Kenji; Worley, Paul F; Bito, Haruhiko.

In: Cell, Vol. 149, No. 4, 11.05.2012, p. 886-898.

Research output: Contribution to journalArticle

Okuno, H, Akashi, K, Ishii, Y, Yagishita-Kyo, N, Suzuki, K, Nonaka, M, Kawashima, T, Fujii, H, Takemoto-Kimura, S, Abe, M, Natsume, R, Chowdhury, S, Sakimura, K, Worley, PF & Bito, H 2012, 'Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ', Cell, vol. 149, no. 4, pp. 886-898. https://doi.org/10.1016/j.cell.2012.02.062
Okuno H, Akashi K, Ishii Y, Yagishita-Kyo N, Suzuki K, Nonaka M et al. Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ. Cell. 2012 May 11;149(4):886-898. https://doi.org/10.1016/j.cell.2012.02.062
Okuno, Hiroyuki ; Akashi, Kaori ; Ishii, Yuichiro ; Yagishita-Kyo, Nan ; Suzuki, Kanzo ; Nonaka, Mio ; Kawashima, Takashi ; Fujii, Hajime ; Takemoto-Kimura, Sayaka ; Abe, Manabu ; Natsume, Rie ; Chowdhury, Shoaib ; Sakimura, Kenji ; Worley, Paul F ; Bito, Haruhiko. / Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ. In: Cell. 2012 ; Vol. 149, No. 4. pp. 886-898.
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