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Neprilysins regulate muscle contraction and heart function via cleavage of SERCA-inhibitory micropeptides

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https://doi.org/10.48693/322
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DC ElementWertSprache
dc.creatorSchiemann, Ronja-
dc.creatorBuhr, Annika-
dc.creatorCordes, Eva-
dc.creatorWalter, Stefan-
dc.creatorHeinisch, Jürgen J.-
dc.creatorFerrero, Paola-
dc.creatorMilting, Hendrik-
dc.creatorPaululat, Achim-
dc.creatorMeyer, Heiko-
dc.date.accessioned2023-05-04T14:36:57Z-
dc.date.available2023-05-04T14:36:57Z-
dc.date.issued2022-07-29-
dc.identifier.citationSchiemann, 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).ger
dc.identifier.urihttps://doi.org/10.48693/322-
dc.identifier.urihttps://osnadocs.ub.uni-osnabrueck.de/handle/ds-202305048979-
dc.description.abstractMuscle 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.eng
dc.relationhttps://doi.org/10.1038/s41467-022-31974-1ger
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCalcium signallingeng
dc.subjectCardiovascular biologyeng
dc.subjectPeptideseng
dc.subjectProteaseseng
dc.subject.ddc570 - Biowissenschaften, Biologieger
dc.titleNeprilysins regulate muscle contraction and heart function via cleavage of SERCA-inhibitory micropeptideseng
dc.typeEinzelbeitrag in einer wissenschaftlichen Zeitschrift [Article]ger
orcid.creatorhttps://orcid.org/0000-0002-5037-9560-
orcid.creatorhttps://orcid.org/0000-0003-4197-4285-
orcid.creatorhttps://orcid.org/0000-0002-5582-642X-
orcid.creatorhttps://orcid.org/0000-0002-8845-6859-
orcid.creatorhttps://orcid.org/0000-0002-3304-4523-
orcid.creatorhttps://orcid.org/0000-0003-2011-2467-
dc.identifier.doi10.1038/s41467-022-31974-1-
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