Calbindin regulates Kv4.1 trafficking and excitability in dentate granule cells via CaMKII-dependent phosphorylation
Open Access
- 7 July 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Experimental & Molecular Medicine
- Vol. 53 (7), 1134-1147
- https://doi.org/10.1038/s12276-021-00645-4
Abstract
Calbindin, a major Ca2+ buffer in dentate granule cells (GCs), plays a critical role in shaping Ca2+ signals, yet how it regulates neuronal function remains largely unknown. Here, we found that calbindin knockout (CBKO) mice exhibited dentate GC hyperexcitability and impaired pattern separation, which co-occurred with reduced K+ current due to downregulated surface expression of Kv4.1. Relatedly, manipulation of calbindin expression in HT22 cells led to changes in CaMKII activation and the level of surface localization of Kv4.1 through phosphorylation at serine 555, confirming the mechanism underlying neuronal hyperexcitability in CBKO mice. We also discovered that Ca2+ buffering capacity was significantly reduced in the GCs of Tg2576 mice to the level of CBKO GCs, and this reduction was restored to normal levels by antioxidants, suggesting that calbindin is a target of oxidative stress. Our data suggest that the regulation of CaMKII signaling by Ca2+ buffering is crucial for neuronal excitability regulation.Keywords
Funding Information
- National Research Foundation of Korea (2017R1A2B2010186, 2020R1A2B5B02002070)
This publication has 59 references indexed in Scilit:
- Lateralization of observational fear learning at the cortical but not thalamic level in miceProceedings of the National Academy of Sciences of the United States of America, 2012
- Detection of an immature dentate gyrus feature in human schizophrenia/bipolar patientsTranslational Psychiatry, 2012
- A βIV-spectrin/CaMKII signaling complex is essential for membrane excitability in miceJCI Insight, 2010
- Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disordersMolecular Brain, 2008
- Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticusEpilepsy Research, 2008
- Dentate Gyrus NMDA Receptors Mediate Rapid Pattern Separation in the Hippocampal NetworkScience, 2007
- Pattern Separation in the Dentate Gyrus and CA3 of the HippocampusScience, 2007
- A computational theory of hippocampal function, and empirical tests of the theoryProgress in Neurobiology, 2006
- Hippocampal conjunctive encoding, storage, and recall: Avoiding a trade‐offHippocampus, 1994
- Computational analysis of the role of the hippocampus in memoryHippocampus, 1994