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

doi:10.1016/j.cell.2012.02.062

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

Deanery of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	886-898
Number of pages	13
Journal	Cell
Volume	149
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2012.02.062
Publication status	Published - 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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10.1016/j.cell.2012.02.062

http://www.sciencedirect.com/science/article/pii/S0092867412004151

Cite this

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, P. F., & 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

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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.",

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

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doi = "10.1016/j.cell.2012.02.062",

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T1 - Inverse Synaptic Tagging of Inactive Synapses via Dynamic Interaction of Arc/Arg3.1 with CaMKIIβ

AU - Okuno, Hiroyuki

AU - Akashi, Kaori

AU - Ishii, Yuichiro

AU - Yagishita-Kyo, Nan

AU - Suzuki, Kanzo

AU - Nonaka, Mio

AU - Kawashima, Takashi

AU - Fujii, Hajime

AU - Takemoto-Kimura, Sayaka

AU - Abe, Manabu

AU - Natsume, Rie

AU - Chowdhury, Shoaib

AU - Sakimura, Kenji

AU - Worley, Paul F

AU - Bito, Haruhiko

PY - 2012/5/11

Y1 - 2012/5/11

N2 - 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.

AB - 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.

KW - Animals

KW - Synapses

KW - Hippocampus

KW - Mice

KW - Dendritic Spines

KW - Mice, Transgenic

KW - Nerve Tissue Proteins

KW - Rats

KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2

KW - Rats, Sprague-Dawley

KW - Cells, Cultured

KW - Neurons

KW - Mice, Inbred C57BL

KW - Cytoskeletal Proteins

U2 - 10.1016/j.cell.2012.02.062

DO - 10.1016/j.cell.2012.02.062

M3 - Article

C2 - 22579289

SN - 1097-4172

VL - 149

SP - 886

EP - 898

JO - Cell

JF - Cell

IS - 4

ER -

Inverse Synaptic Tagging of Inactive Synapses via Dynamic Interaction of Arc/Arg3.1 with CaMKIIβ

Abstract

Keywords / Materials (for Non-textual outputs)

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