PMID- 30142967
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20181211
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 9
DP  - 2018 Aug 23
TI  - The Effect of Ca(2+), Lobe-Specificity, and CaMKII on CaM Binding to Na(V)1.1.
LID - 10.3390/ijms19092495 [doi]
LID - 2495
AB  - Calmodulin (CaM) is well known as an activator of calcium/calmodulin-dependent 
      protein kinase II (CaMKII). Voltage-gated sodium channels (VGSCs) are basic 
      signaling molecules in excitable cells and are crucial molecular targets for 
      nervous system agents. However, the way in which Ca(2+)/CaM/CaMKII cascade 
      modulates Na(V)1.1 IQ (isoleucine and glutamine) domain of VGSCs remains obscure. 
      In this study, the binding of CaM, its mutants at calcium binding sites (CaM(12), 
      CaM(34), and CaM(1234)), and truncated proteins (N-lobe and C-lobe) to Na(V)1.1 
      IQ domain were detected by pull-down assay. Our data showed that the binding of 
      Ca(2+)/CaM to the Na(V)1.1 IQ was concentration-dependent. ApoCaM (Ca(2+)-free 
      form of calmodulin) bound to Na(V)1.1 IQ domain preferentially more than 
      Ca(2+)/CaM. Additionally, the C-lobe of CaM was the predominant domain involved 
      in apoCaM binding to Na(V)1.1 IQ domain. By contrast, the N-lobe of CaM was 
      predominant in the binding of Ca(2+)/CaM to Na(V)1.1 IQ domain. Moreover, 
      CaMKII-mediated phosphorylation increased the binding of Ca(2+)/CaM to Na(V)1.1 
      IQ domain due to one or several phosphorylation sites in T1909, S1918, and T1934 
      of Na(V)1.1 IQ domain. This study provides novel mechanisms for the modulation of 
      Na(V)1.1 by the Ca(2+)/CaM/CaMKII axis. For the first time, we uncover the effect 
      of Ca(2+), lobe-specificity and CaMKII on CaM binding to Na(V)1.1.
FAU - Li, Jianing
AU  - Li J
AD  - Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical 
      University, Shenyang 110122, China. Ariene77687@outlook.com.
FAU - Yu, Zhiyi
AU  - Yu Z
AD  - Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. 
      zhiyi7566@live.cn.
FAU - Xu, Jianjun
AU  - Xu J
AD  - Department of Physiology, Graduate School of Medical and Dental Sciences, 
      Kagoshima University, Kagoshima 890-8544, Japan. jjxuk@m3.kufm.kagoshima-u.ac.jp.
FAU - Feng, Rui
AU  - Feng R
AD  - Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical 
      University, Shenyang 110122, China. fengrui527@163.com.
FAU - Gao, Qinghua
AU  - Gao Q
AD  - Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical 
      University, Shenyang 110122, China. rwygao@m.kufm.kagoshima-u.ac.jp.
AD  - Department of Physiology, Graduate School of Medical and Dental Sciences, 
      Kagoshima University, Kagoshima 890-8544, Japan. rwygao@m.kufm.kagoshima-u.ac.jp.
FAU - Boczek, Tomasz
AU  - Boczek T
AUID- ORCID: 0000-0002-7654-9011
AD  - Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, 
      CA 94305, USA. tomasz.boczek@umed.lodz.pl.
FAU - Liu, Junyan
AU  - Liu J
AD  - Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical 
      University, Shenyang 110122, China. m18602444860_1@163.com.
FAU - Li, Zhi
AU  - Li Z
AD  - Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical 
      University, Shenyang 110122, China. lizhi0824@live.com.
FAU - Wang, Qianhui
AU  - Wang Q
AD  - Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical 
      University, Shenyang 110122, China. WQH91225@163.com.
FAU - Lei, Ming
AU  - Lei M
AD  - Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical 
      University, Shenyang 110122, China. leiming@swmu.edu.cn.
FAU - Gong, Jian
AU  - Gong J
AD  - Department of Clinical Pharmacy, School of Life Science and Biopharmaceutics, 
      Shenyang Pharmaceutical University, Shenyang 110016, China. fanxing1230@163.com.
FAU - Hu, Huiyuan
AU  - Hu H
AD  - Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical 
      University, Shenyang 110122, China. hyhu@cmu.edu.cn.
FAU - Minobe, Etsuko
AU  - Minobe E
AUID- ORCID: 0000-0003-1351-0440
AD  - Department of Physiology, Graduate School of Medical and Dental Sciences, 
      Kagoshima University, Kagoshima 890-8544, Japan. 
      mimiben@m3.kufm.kagoshima-u.ac.jp.
FAU - Ji, Hong-Long
AU  - Ji HL
AUID- ORCID: 0000-0002-3228-7144
AD  - Department of Cellular and Molecular Biology, University of Texas Health Science 
      Center at Tyler, Tyler, TX 75708, USA. james.ji@uthct.edu.
FAU - Kameyama, Masaki
AU  - Kameyama M
AUID- ORCID: 0000-0002-0083-7295
AD  - Department of Physiology, Graduate School of Medical and Dental Sciences, 
      Kagoshima University, Kagoshima 890-8544, Japan. kame@m.kufm.kagoshima-u.ac.jp.
FAU - Guo, Feng
AU  - Guo F
AD  - Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical 
      University, Shenyang 110122, China. blueforest611@hotmail.com.
LA  - eng
GR  - R01 HL134828/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20180823
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Calmodulin)
RN  - 0 (NAV1.1 Voltage-Gated Sodium Channel)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (SCN1A protein, human)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Calcium/*chemistry/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/*chemistry/genetics/metabolism
MH  - Calmodulin/*chemistry/genetics/metabolism
MH  - Cloning, Molecular
MH  - Crystallography, X-Ray
MH  - Escherichia coli/genetics/metabolism
MH  - Gene Expression
MH  - Genetic Vectors/chemistry/metabolism
MH  - Glutathione Transferase/chemistry/genetics/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Kinetics
MH  - Molecular Docking Simulation
MH  - Mutation
MH  - NAV1.1 Voltage-Gated Sodium Channel/*chemistry/genetics/metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Conformation, alpha-Helical
MH  - Protein Conformation, beta-Strand
MH  - Protein Interaction Domains and Motifs
MH  - Recombinant Fusion Proteins/chemistry/genetics/metabolism
MH  - Thermodynamics
PMC - PMC6165294
OTO - NOTNLM
OT  - Ca2+
OT  - CaM
OT  - CaMKII
OT  - IQ domain
OT  - NaV1.1
COIS- The authors declare no conflict of interest.
EDAT- 2018/08/26 06:00
MHDA- 2018/12/12 06:00
PMCR- 2018/09/01
CRDT- 2018/08/26 06:00
PHST- 2018/07/04 00:00 [received]
PHST- 2018/08/06 00:00 [revised]
PHST- 2018/08/13 00:00 [accepted]
PHST- 2018/08/26 06:00 [entrez]
PHST- 2018/08/26 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/09/01 00:00 [pmc-release]
AID - ijms19092495 [pii]
AID - ijms-19-02495 [pii]
AID - 10.3390/ijms19092495 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Aug 23;19(9):2495. doi: 10.3390/ijms19092495.