Calstabin 2: An important regulator for learning and memory in mice

Scientific Reports
Qi YuanGuangju Ji

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.

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Citations

Feb 23, 2019·Proceedings of the National Academy of Sciences of the United States of America·Suzanne M BatisteBjorn C Knollmann
Mar 13, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Kristin F PhillipsLaxmikant S Deshpande
Mar 11, 2020·Molecular Brain·Ren-Wen HanHong-Bo Xin

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Methods Mentioned

BETA
confocal microscopy
Fluorescence

Software Mentioned

MathWorks
Olympus cell R
pClamp
SMART
ImageJ
Origin
CellQuest
MATLAB

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