Titel:	Neprilysins regulate muscle contraction and heart function via cleavage of SERCA-inhibitory micropeptides
Autor(en):	Schiemann, Ronja Buhr, Annika Cordes, Eva Walter, Stefan Heinisch, Jürgen J. Ferrero, Paola Milting, Hendrik Paululat, Achim Meyer, Heiko
ORCID des Autors:	https://orcid.org/0000-0002-5037-9560 https://orcid.org/0000-0003-4197-4285 https://orcid.org/0000-0002-5582-642X https://orcid.org/0000-0002-8845-6859 https://orcid.org/0000-0002-3304-4523 https://orcid.org/0000-0003-2011-2467
Zusammenfassung:	Muscle contraction depends on strictly controlled Ca2+ transients within myocytes. A major player maintaining these transients is the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase, SERCA. Activity of SERCA is regulated by binding of micropeptides and impaired expression or function of these peptides results in cardiomyopathy. To date, it is not known how homeostasis or turnover of the micropeptides is regulated. Herein, we find that the Drosophila endopeptidase Neprilysin 4 hydrolyzes SERCA-inhibitory Sarcolamban peptides in membranes of the sarcoplasmic reticulum, thereby ensuring proper regulation of SERCA. Cleavage is necessary and sufficient to maintain homeostasis and function of the micropeptides. Analyses on human Neprilysin, sarcolipin, and ventricular cardiomyocytes indicates that the regulatory mechanism is evolutionarily conserved. By identifying a neprilysin as essential regulator of SERCA activity and Ca2+ homeostasis in cardiomyocytes, these data contribute to a more comprehensive understanding of the complex mechanisms that control muscle contraction and heart function in health and disease.
Bibliografische Angaben:	Schiemann, R., Buhr, A., Cordes, E. et al. Neprilysins regulate muscle contraction and heart function via cleavage of SERCA-inhibitory micropeptides. Nat Commun 13, 4420 (2022).
URL:	https://doi.org/10.48693/322 https://osnadocs.ub.uni-osnabrueck.de/handle/ds-202305048979
Schlagworte:	Calcium signalling; Cardiovascular biology; Peptides; Proteases
Erscheinungsdatum:	29-Jul-2022
Lizenzbezeichnung:	Attribution 4.0 International
URL der Lizenz:	http://creativecommons.org/licenses/by/4.0/
Publikationstyp:	Einzelbeitrag in einer wissenschaftlichen Zeitschrift [Article]
Enthalten in den Sammlungen:	FB05 - Hochschulschriften Open-Access-Publikationsfonds

Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons