Inducible protein knockout reveals temporal requirement of CaMKII reactivation for memory consolidation in the brain.
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.
Wang
Huimin
H
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
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
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D007700:Kinetics; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016548:Prosencephalon / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D011994:Recombinant Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases