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PMID:22579289

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Citation

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, PF and Bito, H (2012) Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ. Cell 149:886-98

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.

Links

PubMed Online version:10.1016/j.cell.2012.02.062

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:KCC2B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q63053

F

Seeded From UniProt

complete

MOUSE:KCC2B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9WV31

F

Seeded From UniProt

complete

RAT:ARC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P08413

F

Seeded From UniProt

complete

MOUSE:ARC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P28652

F

Seeded From UniProt

complete


See also

References

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