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PXD033492 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleFight-or-flight responses require augmentation of Ca2+ influx via Rad phosphorylation
DescriptionFight-or-flight responses involve β-adrenergic-induced increases in heart rate and contractile force. Despite decades of investigations, predominantly focusing on ryanodine receptor and phospholamban phosphorylation, the molecular mechanisms underlying the sympathetic nervous system control of cardiac contractility remain controversial and incompletely elucidated. Here, we identify the calcium-channel inhibitor Rad as a critical component. In cardiomyocytes isolated from knock-in mice expressing Rad with alanine-substitutions of the four PKA-phosphorylated serine residues (4SA-Rad), calcium currents cannot be increased by adrenergic agonists or phosphatase inhibitor. In these mice, basal cardiac contractility, exercise capacity and heart rate are reduced, and the augmentation of contractile force by adrenergic agonists is severely blunted. Expression of mutant calcium-channel β-subunits that cannot bind Rad is sufficient to restore calcium influx and cardiac contractility in 4SA-Rad mice to levels induced by adrenergic agonists in wild-type mice, revealing a potential therapeutic approach to enhance cardiac contractility while bypassing stimulation of adrenergic receptors.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGary Bradshaw
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListL-methionine sulfone; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-04-28 00:37:00ID requested
12022-09-26 10:41:41announced
Publication List
Dataset with its publication pending
Keyword List
ProteomeXchange project tag: Cardiovascular (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP)
submitter keyword: adrenergic, heart, calcium, ion channels, phosphorylation, contractility, PKA, mass spectrometry, phosphatases
Contact List
Steven O. Marx
contact affiliationDivision of Cardiology, Department of Medicine; Columbia University, Vagelos College of Physicians and Surgeons, 622 West 168th Street, New York, NY 10032. Department of Pharmacology and Molecular Signaling, Columbia University, Vagelos College of Physicians and Surgeons
contact emailsm460@cumc.columbia.edu
lab head
Gary Bradshaw
contact affiliationHarvard Medical School
contact emailGary_bradshaw@hms.harvard.edu
dataset submitter
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Dataset FTP location
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