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


ABSTRACT: By integrating convergent protein engineering and rational inhibitor design, we have developed an in vivo conditional protein knockout andor 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 alpha-Ca(2+)calmodulin-dependent protein kinase II (alphaCAMKII), 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.

SUBMITTER: Wang H 

PROVIDER: S-EPMC153085 | biostudies-literature | 2003 Apr

REPOSITORIES: biostudies-literature

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

Wang Huimin H   Shimizu Eiji E   Tang Ya-Ping YP   Cho Min M   Kyin Maureen M   Zuo Wenqi W   Robinson Daphne A DA   Alaimo Peter J PJ   Zhang Chao C   Morimoto Hiromi H   Zhuo Min M   Feng Ruiben R   Shokat Kevan M KM   Tsien Joe Z JZ  

Proceedings of the National Academy of Sciences of the United States of America 20030319 7


By integrating convergent protein engineering and rational inhibitor design, we have developed an in vivo conditional protein knockout andor 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 alpha-Ca(2+)calmodulin-dependent protein kinase II (alphaCAMKII), on th  ...[more]

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