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doi:10.22028/D291-47595 | Title: | NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart |
| Author(s): | 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 Steinmetz, Lars M Meder, Benjamin |
| Language: | English |
| Title: | Nature Communications |
| Volume: | 13 |
| Issue: | 1 |
| Publisher/Platform: | Springer Nature |
| Year of Publication: | 2022 |
| Free key words: | Cardiovascular biology Phosphorylation |
| DDC notations: | 610 Medicine and health |
| Publikation type: | Journal Article |
| Abstract: | To adapt to changing hemodynamic demands, regulatory mechanisms mod ulate actin-myosin-kinetics by calcium-dependent and-independent mechanisms. We investigate the posttranslational modification of human essential myosinlightchain(ELC)andidentifyNIMA-relatedkinase9(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. |
| DOI of the first publication: | 10.1038/s41467-022-33658-2 |
| URL of the first publication: | https://doi.org/10.1038/s41467-022-33658-2 |
| Link to this record: | urn:nbn:de:bsz:291--ds-475953 hdl:20.500.11880/41618 http://dx.doi.org/10.22028/D291-47595 |
| ISSN: | 2041-1723 |
| Date of registration: | 28-Apr-2026 |
| Description of the related object: | Supplementary information |
| Related object: | https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-33658-2/MediaObjects/41467_2022_33658_MOESM1_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-33658-2/MediaObjects/41467_2022_33658_MOESM2_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-33658-2/MediaObjects/41467_2022_33658_MOESM3_ESM.mp4 https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-33658-2/MediaObjects/41467_2022_33658_MOESM4_ESM.mp4 https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-33658-2/MediaObjects/41467_2022_33658_MOESM5_ESM.mp4 https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-33658-2/MediaObjects/41467_2022_33658_MOESM6_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-33658-2/MediaObjects/41467_2022_33658_MOESM7_ESM.pdf |
| Faculty: | M - Medizinische Fakultät |
| Department: | M - Medizinische Biometrie, Epidemiologie und medizinische Informatik |
| Professorship: | M - Univ.-Prof. Dr. Andreas Keller |
| Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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| File | Description | Size | Format | |
|---|---|---|---|---|
| s41467-022-33658-2.pdf | 3,09 MB | Adobe PDF | View/Open |
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