PXD027738-1

PXD027738 is an original dataset announced via ProteomeXchange.

Title	Neprilysins regulate muscle contraction and heart function via cleavage of SERCA-inhibitory micropeptides
Description	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. We found that the Drosophila endopeptidase Neprilysin 4 hydrolyzes SERCA-inhibitory Sarcolamban peptides in membranes of the sarcoplasmic reticulum, thereby ensuring proper regulation of SERCA. Cleavage was necessary and sufficient to maintain homeostasis and function of the micropeptides. Analyses on human Neprilysin, sarcolipin, and ventricular cardiomyocytes indicated 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.
HostingRepository	PRIDE
AnnounceDate	2022-06-01
AnnouncementXML	Submission_2022-06-01_02:51:43.519.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Heiko Meyer
SpeciesList	scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-05 08:59:44	ID requested
⏵ 1	2022-06-01 02:51:43	announced

Dataset with its publication pending

submitter keyword: SERCA, Neprilysin, metallopeptidase, micropeptides, heart physiology, calcium homeostasis, Drosophila melanogaster

Heiko Meyer
contact affiliation	Heiko Meyer, Osnabruck University, Department of Zoology / Developmental Biology, Barbarastr. 11, 49076 Osnabruck, Germany
contact email	Meyer@biologie.uni-osnabrueck.de
lab head
Heiko Meyer
contact affiliation	University of Osnabruck Barbarastr 11 49076 Osnabruck
contact email	Meyer@biologie.uni-osnabrueck.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027738
     1. Label: PRIDE project
     2. Name: Neprilysins regulate muscle contraction and heart function via cleavage of SERCA-inhibitory micropeptides