Inducible protein knockout reveals temporal requirement of CaMKII reactivation for memory consolidation in the brain

Huimin Wang, Eiji Shimizu, Ya Ping Tang, Min Cho, Maureen Kyin, Wenqi Zuo, Daphne A. Robinson, Peter J. Alaimo, Chao Zhang, Hiromi Morimoto, Min Zhuo, Ruiben Feng, Kevan M. Shokat, Joe Z. Tsien

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128 Scopus citations

Abstract

By integrating convergent protein engineering and rational inhibitor design, we have developed an in vivo conditional protein knockout and/or manipulation technology. This method is based on the creation of a specific interaction interface between a modified protein domain and sensitized inhibitors. By introducing this system into genetically modified mice, we can readily manipulate the activity of a targeted protein, such as α-Ca2+/calmodulin-dependent protein kinase II (αCAMKII), on the time scale of minutes in specific brain subregions of freely behaving mice. With this inducible and region-specific protein knockout technique, we analyzed the temporal stages of memory consolidation process and revealed the first postlearning week as the critical time window during which a precise level of CaMKII reactivation is essential for the consolidation of long-term memories in the brain.

Original languageEnglish (US)
Pages (from-to)4287-4292
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number7
DOIs
StatePublished - Apr 1 2003

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    Wang, H., Shimizu, E., Tang, Y. P., Cho, M., Kyin, M., Zuo, W., Robinson, D. A., Alaimo, P. J., Zhang, C., Morimoto, H., Zhuo, M., Feng, R., Shokat, K. M., & Tsien, J. Z. (2003). Inducible protein knockout reveals temporal requirement of CaMKII reactivation for memory consolidation in the brain. Proceedings of the National Academy of Sciences of the United States of America, 100(7), 4287-4292. https://doi.org/10.1073/pnas.0636870100