title: Calstabin 2: An important regulator for learning and memory in mice.
abstract: Calstabin2, also named FK506 binding protein 12.6 (FKBP12.6), is a subunit of ryanodine receptor subtype 2 (RyR2) macromolecular complex, which is an intracellular calcium channel and abundant in the brain. Previous studies identified a role of leaky neuronal RyR2 in posttraumatic stress disorder (PTSD). However, the functional role of Calstabin2 in the cognitive function remains unclear. Herein, we used a mouse model of genetic deletion of Calstabin2 to investigate the function of Calstabin2 in cognitive dysfunction. We found that Calstabin2 knockout (KO) mice showed significantly reduced performance in Morris Water Maze (MWM), long-term memory (LTM) contextual fear testing, and rotarod test when compared to wild type (WT) littermates. Indeed, genetic deletion of Calstabin2 reduced long-term potentiation (LTP) at the hippocampal CA3-CA1 connection, increased membrane excitability, and induced RyR2 leak. Finally, we demonstrated that the increase in cytoplasmic calcium activated Ca(2+) dependent potassium currents and led to neuronal apoptosis in KO hippocampal neurons. Thus, these results suggest that neuronal RyR2 Ca(2+) leak due to Calstabin2 deletion contributes to learning deficiency and memory impairment.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|Department of Physiology and Cellular Biophysics, Columbia University, New York, New York 10032, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang 330000, China.
authors.forename: Ke-Yu
authors.initials: KY
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Brian and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Le
authors.initials: L
authors.lastname: Sun
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Chi
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang 330000, China.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Xin
authors.affiliation: State Key Laboratory of Brian and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Wang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Guangju
authors.initials: G
authors.lastname: Ji
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D022021:Tacrolimus Binding Proteins; C509259:FKBP1B protein, mouse