title: 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.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Huimin
authors.initials: H
authors.lastname: Wang
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Tang
authors.forename: Min
authors.initials: M
authors.lastname: Cho
authors.forename: Maureen
authors.initials: M
authors.lastname: Kyin
authors.forename: Wenqi
authors.initials: W
authors.lastname: Zuo
authors.forename: Daphne A
authors.initials: DA
authors.lastname: Robinson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Alaimo
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Hiromi
authors.initials: H
authors.lastname: Morimoto
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
authors.forename: Ruiben
authors.initials: R
authors.lastname: Feng
authors.forename: Kevan M
authors.initials: KM
authors.lastname: Shokat
authors.forename: Joe Z
authors.initials: JZ
authors.lastname: Tsien
mesh_terms: 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
chemical_list: D011994:Recombinant Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases