The role of CaMKII-Tiam1 complex on learning and memory
Neurobiology of Learning and Memory. 2019-12-01; 166: 107070
DOI: 10.1016/j.nlm.2019.107070
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Kojima H(1), Rosendale M(2), Sugiyama Y(3), Hayashi M(4), Horiguchi Y(4),
Yoshihara T(4), Ikegaya Y(5), Saneyoshi T(6), Hayashi Y(7).
Author information:
(1)Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical
Sciences, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-0033, Japan;
Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto
606-8501, Japan; RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
(2)Department of Pharmacology, Graduate School of Medicine, Kyoto University,
Kyoto 606-8501, Japan; RIKEN Brain Science Institute, Wako, Saitama 351-0198,
Japan.
(3)Department of Pharmacology, Graduate School of Medicine, Kyoto University,
Kyoto 606-8501, Japan.
(4)Institute of Laboratory Animals, Graduate School of Medicine, Kyoto
University, Kyoto 606-8501, Japan.
(5)Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical
Sciences, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-0033, Japan.
(6)Department of Pharmacology, Graduate School of Medicine, Kyoto University,
Kyoto 606-8501, Japan; RIKEN Brain Science Institute, Wako, Saitama 351-0198,
Japan. Electronic address: .
(7)Department of Pharmacology, Graduate School of Medicine, Kyoto University,
Kyoto 606-8501, Japan; RIKEN Brain Science Institute, Wako, Saitama 351-0198,
Japan. Electronic address: .
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
Tiam1, an activator of the small G-protein Rac1, locks CaMKII into an active
conformation, which in turn maintains the phosphorylation status of Tiam1. This
makes Rac1 persistently active, specifically in the stimulated spine. To
understand the significance of the CaMKII-Tiam1 RAKEC in vivo, we generated a
Tiam1 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 Rac1 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-Tiam1 interaction
regulates spine morphology in vivo and is required for memory storage.
Copyright © 2019 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.nlm.2019.107070
PMID: 31445077 [Indexed for MEDLINE]