Journal
NEUROBIOLOGY OF LEARNING AND MEMORY
Volume 166, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nlm.2019.107070
Keywords
Reciprocally activating kinase-effector complex; Synaptic plasticity; Ca2+/calmodlin-dependent protein kinase II; Actin; Guanine-nucleotide exchange factor; Behaviour battery
Funding
- JSPS
- RIKEN, JSPS, Japan [20240032, 16H02455, 22110006, 16F16712, 18H04733, 18H05434, 24680036, 25113726, 23113522, 18H02528, 18K19377]
- Human Frontier Science Programme
- Uehara Memorial Foundation
- Naito Foundation
- Takeda Science Foundation
- Japan Foundation for Applied Enzymology
- Novartis Foundation (Japan) for the Promotion of Science
- Research Foundation for Opto-Science and Technology
- Brain Science Foundation, Japan
- Kyoto University Foundation
- Shimadzu Science Foundation
- Pharmacological Research Foundation
- RIKEN
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A stimulation inducing long-term potentiation (LTP) of synaptic transmission induces a persistent expansion of dendritic spines, a phenomenon known as structural LTP (sLTP). We previously proposed that the formation of a reciprocally activating kinase-effector complex (RAKEC) between CaMKII and Tiaml, an activator of the small G-protein Racl, locks CaMKII into an active conformation, which in turn maintains the phosphorylation status of Tiaml. This makes Racl persistently active, specifically in the stimulated spine. To understand the significance of the CaMKII-Tiaml RAKEC in vivo, we generated a Tiaml mutant knock-in mouse line in which critical residues for CaMKII binding were mutated into alanines. We confirmed the central role of this interaction on sLTP by observing that KI mice showed reduced Racl activity, had smaller spines and a diminished sLTP as compared to their wild-type littermates. Moreover, behavioral tests showed that the novel object recognition memory of these animals was impaired. We thus propose that the CaMKII-Tiaml interaction regulates spine morphology in vivo and is required for memory storage.
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