Structure of calcium/calmodulin-dependent protein kinase type Ⅱ and its role in nervous system

WANG Tong-tong CHEN Zhi-chi YE Xin FU Wei-da CHEN Meng-jiao LI Jun-nan SUN Chen-you*

doi:10.16098/j.issn.0529-1356.2019.03.022

PDF(863 KB)

Acta Anatomica Sinica ›› 2019, Vol. 50 ›› Issue (3) : 395-399. DOI: 10.16098/j.issn.0529-1356.2019.03.022

Review

Structure of calcium/calmodulin-dependent protein kinase type Ⅱ and its role in nervous system

WANG Tong-tong ^1,2 CHEN Zhi-chi^1,2 YE Xin^1,2 FU Wei-da³ CHEN Meng-jiao³ LI Jun-nan³SUN Chen-you ^1,2*

Author information +

History +

Abstract

Calcium (Ca²⁺ ) has long been recognized as a crucial intracellular messenger attaining stimuli specific cellular outcomes via localized signaling. Ca²⁺ binding proteins, such as calmodulin (CaM) and its target proteins are key to Ca²⁺ -dependent signaling events. Calcium/calmodulin-dependent protein kinase type Ⅱ (CaMKⅡ) is a highly abundant polymer enzyme comprising a significant fraction of total protein in mammalian forebrain and forming a major component of the postsynaptic density. In recent years, studies have shown that CaMKⅡ contains four subtypes of α, β, γ and δ, in which CaMKⅡ α and β are mainly expressed in nerve tissues and γ and δ are expressed in the whole body. They are essential for certain synaptic plasticity and memory consolidation processes, both in the central nervous system and in the excitability of the nervous system and in some neurological diseases. CaMKⅡ may play an important role in the pathogenesis of some nervous system diseases. Previous studies have also shown tha CaMKⅡδ plays an important role in promoting neuronal survival. The structure of CaMKⅡ and its role in nervous system and its relationship with related nervous system diseases will be reviewed.

Key words

Calcium / Calmodulin / Calcium/calmodulin-dependent protein kinase type Ⅱ

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

WANG Tong-tong CHEN Zhi-chi YE Xin FU Wei-da CHEN Meng-jiao LI Jun-nan SUN Chen-you. Structure of calcium/calmodulin-dependent protein kinase type Ⅱ and its role in nervous system[J]. Acta Anatomica Sinica. 2019, 50(3): 395-399 https://doi.org/10.16098/j.issn.0529-1356.2019.03.022

References

［1］ Young LM, Geldenhuys WJ, Domingo OC, et al. Synthesis and biological evaluation of pentacycloundecylamines and triquinylamines as voltage-gated calcium channel blockers［J］. Arch Pharm (Weinheim), 2016，349(4):252-267.
［2］ Dore K, Stein IS, Brock JA,et al. Unconventional NMDA receptor signaling［J］. J Neurosci, 2017, 37 (45):10800-10807.
［3］ Wang JH, Cui S. Neuronal signal encoding and storage as principles of brain function［J］. Prog Biochem Biophys, 2016,43(4):367-373.
［4］ Milosevic A, Noctor SC, Martinez-Cerdeno Ⅴ,et al. Progenitors from the postnatal forebrain subventricular zone differentiate into cerebellar-like interneurons and cerebellar-specific astrocytes upon transplantation［J］. Mol Cell Neurosci, 2008,39(3): 324-334.
［5］ Incontro S, Díaz-Alonso J, Iafrati J, et al. The CaMKⅡ/NMDA receptor complex controls hippocampal synaptic transmission by kinase-dependent and independent mechanisms［J］. Nat Commun, 2018, 9(1):2069.
［6］ Poon AD, McGill SH, Bhupanapadu Sunkesula SR, et al. Ca2+/calmodulin-dependent protein kinase Ⅱ and Dimethyl Sulfoxide affect the sealing frequencies of transected hippocampal neurons［J］. J Neurosci Res, 2018, 96(7): 1208-1222.
［7］ Goodell, DJ, Benke TA, Bayer KU. Developmental restoration of LTP deficits in heterozygous CaMKⅡ alpha KO mice［J］. J Neurophysiol, 2016, 116(5):2140-2151.
［8］ Moriguchi S, Kita S, Fukaya M,et al. Reduced expression of Na+/Ca2+ exchangers is associated with cognitive deficits seen in Alzheimer’s disease model mice［J］. Neuropharmacology, 2018, 131: 291-303.
［9］ Takemoto-Kimura S, Suzuki K, Horigane SI, et al. Calmodulin kinases: essential regulators in health and disease［J］. J Neurochem, 2017,141(6): 808-818.
［10］ Gray CB, Heller Brown J. CaMKⅡdelta subtypes: localization and function［J］. Front Pharmacol, 2014,5:15.
［11］ Srinivasan M, Edman CF, Schulman H. Alternative splicing introduces a nuclear localization signal that targets multifunctional CaM kinase to the nucleus［J］. J Cell Biol, 126(4): 839-852.
［12］ Schworer CM, Rothblum LI, Thekkumkara TJ, et al. Identification of novel isoforms of the delta subunit of Ca2+/calmodulin-dependent protein kinase Ⅱ. Differential expression in rat brain and aorta［J］. J Biol Chem, 1993, 268(19):14443-14449.
［13］ Shioda N, Fukunaga K. Physiological and pathological roles of CaMKⅡ-PP1 signaling in the Brain［J］. Int J Mol Sci,2018,19(11):20.
［14］ Sobhia ME, Grewal BK, Paul ML,et al. Protein kinase C inhibitors: a patent review (2010-present)［J］. Expert Opin Ther Pat, 2013, 23(11): 1451-1468. 
［15］ Shi J, Zhang XK, Yin L, et al. Herbal formula GAPT prevents beta amyloid deposition induced Ca2+/Calmodulin-dependent protein kinase Ⅱ and Ca2+/calmodulin-dependent protein phosphatase 2B imbalance in APPV717I mice［J］. BMC Complement Altern Med, 2016, 16:159.
［16］ Ashpole NM, Song W, Brustovetsky T, et al. Calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) inhibition induces neurotoxicity via dysregulation of glutamate/calcium signaling and hyperexcitability［J］. J Biol Chem, 2012, 287(11): 8495-8506.
［17］ Pullara F, Asciutto EK, General IJ. Mechanisms of activation and subunit release in Ca2+/calmodulin-dependent protein kinase Ⅱ［J］. J Phys Chem B, 2017, 121(45):10344-10352.
［18］ O’Brien MT, Oakhill JS, Ling NX,et al. Impact of genetic variation on CaMKK2 regulation by Ca2+ -calmodulin and multisite phosphorylation［J］. Sci Rep, 2017, 7: 43264.
［19］ Lucic Ⅴ, Greif GJ, Kennedy MB. Detailed state model of CaMKⅡ activation and autophosphorylation［J］. Eur Biophys J, 2008, 38(1):83-98.
［20］ Baek A, Park EJ, Kim SY,et al. High-frequency repetitive magnetic stimulation enhances the expression of brain-derived neurotrophic factor through activation of Ca2+ -calmodulin-dependent protein kinase Ⅱ-cAMP-response element-binding protein pathway［J］. Front Neurol, 2018, 9:285
［21］ Sasi M, Vignoli B, Canossa M, et al. Neurobiology of local and intercellular BDNF signaling［J］. Pflugers Arch, 2017,469(56): 593-610.
［22］ Kamata A, Takeuchi Y, Fukunaga K. Identification of the isoforms of Ca2+/calmodulin-dependent protein kinase Ⅱ and expression of brain-derived neurotrophic factor mRNAs in the substantia nigra［J］. J Neurochem, 2006, 96(1): 195-203.
［23］ Dewenter M, von der Lieth A, Katus HA, et al. Calcium signaling and transcriptional regulation in cardiomyocytes［J］. Circ Res, 2017,121(8):1000-1020.
［24］ Abbasi WA, Asif A, Andleeb S,et al. CaMELS: in silico prediction of calmodulin binding proteins and their binding sites［J］. Proteins, 2017,85(9):1724-1740.
［25］ Tomasetti C, Iasevoli F, Buonaguro EF, et al. Treating the synapse in major psychiatric disorders: the role of postsynaptic density network in dopamine-glutamate interplay and psychopharmacologic drugs molecular actions［J］. Int J Mol Sci, 2017,18(1):135.
［26］ Woods NK, Padmanabhan J. Neuronal calcium signaling and Alzheimer’s disease ［J］. Adv Exp Med Biol, 2012, 740: 1193-1217.
［27］ Pasek JG, Wang XH, Colbran RJ. Differential CaMKⅡ regulation by voltage-gated calcium channels in the striatum［J］. Mol Cell Neurosci, 2015, 68:234-243.
［28］ Churn SB, Rana A, Lee K, et al.Calcium/calmodulin-dependent kinase Ⅱ phosphorylation of the GABA(A) receptor alpha 1 subunit modulates benzodiazepine binding［J］. J Neurochem, 2002,82(5):1065-1076.
［29］ Demir S, Bagirici F, Marangoz C. A calcium channel blocker nicardipine protects neurons from zinc - induced toxicity in rat hippocampus［J］. Neurosci Res Commun, 2002, 30(3): 135-141.
［30］ Liu XB, Murray KD. Neuronal excitability and calcium/calmodulin-dependent protein kinase type Ⅱ: location, location, location［J］. Epilepsia, 2012,53:45-52.
［31］ Ghosh A, Giese KP. Calcium/calmodulin-dependent kinase Ⅱ and Alzheimer’s disease［J］. Mol Brain, 2015, 8(1):78.
［32］ Oka M, Fujisaki N, Maruko-Otake A, et al. Ca2+/calmodulin-dependent protein kinase Ⅱ promotes neurodegeneration caused by tau phosphorylated at Ser262/356 in a transgenic Drosophila model of tauopathy［J］. J Biochem, 2017,162(5):335-342.
［33］ Min D, Guo F, Zhu S, et al. The alterations of Ca2+/calmodulin/CaMKⅡ/CaV1.2 signaling in experimental models of Alzheimer’s disease and vascular dementia［J］. Neurosci Lett,2013, 538:60-65.