NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart. Müller, M., Eghbalian, R., Boeckel, J., Frese, K., Haas, J., Kayvanpour, E., Sedaghat-Hamedani, F., Lackner, M., Tugrul, O., Ruppert, T., Tappu, R., Bordalo, D., Kneuer, J., Piekarek, A., Herch, S., Schudy, S., Keller, A., Grammes, N., Bischof, C., & Meder, B. Nature Communications, 13:6209, 10, 2022.
NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart [link]Paper  doi  abstract   bibtex   
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. Phosphorylation of the essential myosin light chain (ELC) influence actin-myosin crossbridge cycling in the heart. Here, the authors show upregulated ELC-phosphorylation in systolic heart failure and identify NIMArelated kinase 9 to bind to ELC mediating its calcium-dependent phosphorylation.
@article{nima2022,
	author = {Müller, Marion and Eghbalian, Rose and Boeckel, Jes-Niels and Frese, Karen and Haas, Jan and Kayvanpour, Elham and Sedaghat-Hamedani, Farbod and Lackner, Maximilian and Tugrul, Oguz and Ruppert, Thomas and Tappu, Rewati and Bordalo, Diana and Kneuer, Jasmin and Piekarek, Annika and Herch, Sabine and Schudy, Sarah and Keller, Andreas and Grammes, Nadja and Bischof, Cornelius and Meder, Benjamin},
	year = {2022},
	month = {10},
    	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. Phosphorylation of the essential myosin light chain (ELC) influence actin-myosin crossbridge cycling in the heart. Here, the authors show upregulated ELC-phosphorylation in systolic heart failure and identify NIMArelated kinase 9 to bind to ELC mediating its calcium-dependent phosphorylation.}",
	pages = {6209},
	title = {NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart},
	volume = {13},
	journal = {Nature Communications},
    	url = {https://doi.org/10.1038/s41467-022-33658-23},
	doi = {10.1038/s41467-022-33658-2}
}

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