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 language | English (US) |
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Pages (from-to) | 4287-4292 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 100 |
Issue number | 7 |
DOIs | |
State | Published - Apr 1 2003 |
Externally published | Yes |
ASJC Scopus subject areas
- General