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 journalArticlepeer-review

Abstract / Description of output

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
Pages (from-to)886-898
Number of pages13
Issue number4
Publication statusPublished - 11 May 2012

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Synapses
  • Hippocampus
  • Mice
  • Dendritic Spines
  • Mice, Transgenic
  • Nerve Tissue Proteins
  • Rats
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Rats, Sprague-Dawley
  • Cells, Cultured
  • Neurons
  • Mice, Inbred C57BL
  • Cytoskeletal Proteins


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