title: Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ.
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.
authors.affiliation: Department of Neurochemistry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan. okuno@m.u-tokyo.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okuno
authors.forename: Kaori
authors.initials: K
authors.lastname: Akashi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ishii
authors.forename: Nan
authors.initials: N
authors.lastname: Yagishita-Kyo
authors.forename: Kanzo
authors.initials: K
authors.lastname: Suzuki
authors.forename: Mio
authors.initials: M
authors.lastname: Nonaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawashima
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujii
authors.forename: Sayaka
authors.initials: S
authors.lastname: Takemoto-Kimura
authors.forename: Manabu
authors.initials: M
authors.lastname: Abe
authors.forename: Rie
authors.initials: R
authors.lastname: Natsume
authors.forename: Shoaib
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.forename: Paul F
authors.initials: PF
authors.lastname: Worley
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Bito
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2