Inverse Synaptic Tagging of Inactive Synapses via Dynamic Interaction of Arc/Arg3.1 with CaMKII¦Â

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• 作者：Hiroyuki Okuno¹ ; ⁶ ; ^{okuno@m.u-tokyo.ac.jp} ; Kaori Akashi³ ; Yuichiro Ishii¹ ; ² ; Nan Yagishita-Kyo¹ ; ² ; Kanzo Suzuki¹ ; ² ; Mio Nonaka¹ ; ² ; ⁶ ; Takashi Kawashima¹ ; ² ; Hajime Fujii¹ ; ⁶ ; Sayaka Takemoto-Kimura¹ ; ⁴ ; Manabu Abe³ ; Rie Natsume³ ; Shoaib Chowdhury⁵ ; Kenji Sakimura³ ; ⁶ ; Paul  ; F. Worley⁵ ; Haruhiko Bito¹ ; ² ; ⁶ ; ^{hbito@m.u-tokyo.ac.jp}
• 刊名：Cell
• 出版年：2012
• 出版时间：11 May, 2012
• 年：2012
• 卷：149
• 期：4
• 页码：886-898
• 全文大小：1968 K

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Summary

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 CaMKII¦Â 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 CaMKII¦Â 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.