PUBLICATION

NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart

Authors
Müller, M., Eghbalian, R., Boeckel, J.N., Frese, K.S., Haas, J., Kayvanpour, E., Sedaghat-Hamedani, F., Lackner, M.K., Tugrul, O.F., Ruppert, T., Tappu, R., Martins Bordalo, D., Kneuer, J.M., Piekarek, A., Herch, S., Schudy, S., Keller, A., Grammes, N., Bischof, C., Klinke, A., Cardoso-Moreira, M., Kaessmann, H., Katus, H.A., Frey, N., Steinmetz, L.M., Meder, B.
ID
ZDB-PUB-221022-1
Date
2022
Source
Nature communications   13: 6209 (Journal)
Registered Authors
Frese, Karen, Meder, Benjamin, Müller, Marion
Keywords
none
MeSH Terms
  • Protein Kinases/metabolism
  • Humans
  • Actins*/metabolism
  • Phosphorylation
  • Animals
  • NIMA-Related Kinases/genetics
  • NIMA-Related Kinases/metabolism
  • Zebrafish/metabolism
  • Myosin Light Chains*/metabolism
  • Calcium/metabolism
(all 10)
PubMed
36266340 Full text @ Nat. Commun.
Abstract
To adapt to changing hemodynamic demands, regulatory mechanisms modulate actin-myosin-kinetics by calcium-dependent and -independent mechanisms. We investigate the posttranslational modification of human essential myosin light chain (ELC) and identify NIMA-related kinase 9 (NEK9) to interact with ELC. NEK9 is highly expressed in the heart and the interaction with ELC is calcium-dependent. Silencing of NEK9 results in blunting of calcium-dependent ELC-phosphorylation. CRISPR/Cas9-mediated disruption of NEK9 leads to cardiomyopathy in zebrafish. Binding to ELC is mediated via the protein kinase domain of NEK9. A causal relationship between NEK9 activity and ELC-phosphorylation is demonstrated by genetic sensitizing in-vivo. Finally, we observe significantly upregulated ELC-phosphorylation in dilated cardiomyopathy patients and provide a unique map of human ELC-phosphorylation-sites. In summary, NEK9-mediated ELC-phosphorylation is a calcium-dependent regulatory system mediating cardiac contraction and inotropy.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
m647
    		Point Mutation
    uh11
      		Indel
      uh12
        		Indel
          1 - 3 of 3
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          ilkMO1-ilkMRPHLNO
          nek9CRISPR1-nek9CRISPR
          nek9CRISPR2-nek9CRISPR
          nek9CRISPR3-nek9CRISPR
          nek9MO1-nek9MRPHLNO
          nek9MO2-nek9MRPHLNO
          tyrCRISPR1-tyrCRISPR
          1 - 7 of 7
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          Fish
          No data available
          Antibodies
          No data available
          Orthology
          Engineered Foreign Genes
          No data available
          Mapping
          No data available
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          Citation
          Müller, M., Eghbalian, R., Boeckel, J.N., Frese, K.S., Haas, J., Kayvanpour, E., Sedaghat-Hamedani, F., Lackner, M.K., Tugrul, O.F., Ruppert, T., Tappu, R., Martins Bordalo, D., Kneuer, J.M., Piekarek, A., Herch, S., Schudy, S., Keller, A., Grammes, N., Bischof, C., Klinke, A., Cardoso-Moreira, M., Kaessmann, H., Katus, H.A., Frey, N., Steinmetz, L.M., Meder, B. (2022) NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart. Nature communications. 13:6209.