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Müller, Marion; Eghbalian, Rose; Boeckel, Jes-Niels; Frese, Karen S.; Haas, Jan; Kayvanpour, Elham; Sedaghat-Hamedani, Farbod; Lackner, Maximilian K.; Tugrul, Oguz F.; Ruppert, Thomas; Tappu, Rewati; Martins Bordalo, Diana; Kneuer, Jasmin M.; Piekarek, Annika; Herch, Sabine; Schudy, Sarah; Keller, Andreas; Grammes, Nadja; Bischof, Cornelius; Klinke, Anna; Cardoso-Moreira, Margarida; Kaessmann, Henrik; Katus, Hugo A.; Frey, Norbert; [...]

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

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  • Media type: E-Article
  • Title: NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart
  • Contributor: Müller, Marion; Eghbalian, Rose; Boeckel, Jes-Niels; Frese, Karen S.; Haas, Jan; Kayvanpour, Elham; Sedaghat-Hamedani, Farbod; Lackner, Maximilian K.; Tugrul, Oguz F.; Ruppert, Thomas; Tappu, Rewati; Martins Bordalo, Diana; Kneuer, Jasmin M.; Piekarek, Annika; Herch, Sabine; Schudy, Sarah; Keller, Andreas; Grammes, Nadja; Bischof, Cornelius; Klinke, Anna; Cardoso-Moreira, Margarida; Kaessmann, Henrik; Katus, Hugo A.; Frey, Norbert; [...]
  • imprint: Springer Science and Business Media LLC, 2022
  • Published in: Nature Communications
  • Language: English
  • DOI: 10.1038/s41467-022-33658-2
  • ISSN: 2041-1723
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>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.</jats:p>
  • Access State: Open Access