@article{dc7fce331fe242e0891ca83ca036abfd,
title = "Inverse Synaptic Tagging of Inactive Synapses via Dynamic Interaction of Arc/Arg3.1 with CaMKII beta",
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 CaMKII beta 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 beta 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.",
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",
note = "We thank H. Schulman and T. Meyer for several CaMKII constructs, R.Y. Tsien for mCherry cDNA, A. Miyawaki for Venus cDNA, M. Yamamoto for GFP-TeNT cDNA, K.U. Bayer for pmEGFP-CaMKIIβe cDNA, and M. Watanabe for an anti-vGlut1 antibody, and all members of the Bito laboratory for support. BDNF was provided by Dainippon Sumitomo Pharma, Osaka, Japan. We thank T. Bonhoeffer, K. Deisseroth, R.G.M. Morris, V. Naegerl, R. Redondo, M. van Rossum, M. Schnitzer, and R.W. Tsien for valuable comments on an earlier version of this work, and R. Huganir for critical reading of the manuscript. We are indebted to Y. Kondo, K. Saiki, A. Adachi-Morishima, R. Gyobu, and T. Kinbara for assistance. This work was supported in part by Grants-in-Aid (WAKATE, KIBAN, START, CBSN) from JSPS and MEXT of Japan (to H.O., M.N., S.T-K., K. Sakimura, and H.B.), from the MHLW of Japan (to H.O. and H.B.), by a grant from NIMH (to P.F.W.), and by awards from the HFSP (to H.O. and H.B.) and from the Shimadzu Foundation, Kowa Life Science Foundation, Takeda Science Foundation, and the Mitsubishi Foundation (to H.B.). Y.I., N.Y-K., K. Suzuki, and T.K. are JSPS predoctoral fellows.",
year = "2012",
month = may,
day = "11",
doi = "10.1016/j.cell.2012.02.062",
language = "الإنجليزيّة",
volume = "149",
pages = "886--898",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "4",
}