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PXD016483

PXD016483 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe β2-subunit of voltage-gated calcium channels inhibits cardiomyocyte hypertrophy through a channel-independent mechanism.
DescriptionL-type voltage-gated calcium channels (LTCCs) regulate crucial physiological processes in the heart. They are composed of the Cav1 pore-forming subunit and the accessory subunits Cav, Cav2 and Cav. Cav is a cytosolic soluble protein that regulates channel trafficking and activity, but it also exerts other LTCC-independent functions. Cardiac hypertrophy, a relevant risk factor for the development of congestive heart failure, depends on the activation of calcium-dependent pro-hypertrophic signaling cascades; however, the role of LTCCs in this pathology remains controversial. Here, by using shRNA-mediated Cav silencing, we demonstrate that Cav2 downregulation enhances 1-adrenergic receptor agonist-induced cardiomyocyte hypertrophy in an LTCC-independent manner. We report that a pool of Cav2 is targeted to the nucleus in cardiomyocytes and that the expression of this nuclear fraction decreases during in vitro and in vivo induction of cardiac hypertrophy. Moreover, the overexpression of nucleus-targeted Cav2 in cardiomyocytes inhibits in vitro-induced hypertrophy. Quantitative proteomic analyses showed that Cav2 knockdown leads to changes in the expression of diverse myocyte proteins, including reduction of calpastatin, an endogenous inhibitor of the calcium-dependent protease calpain. Accordingly, Cav2-deficient cardiomyocytes had a two-fold increase in calpain activity as compared to control cells. Furthermore, inhibition of calpain activity in Cav2-deficient cells abolished the enhanced 1-adrenergic receptor agonist-induced hypertrophy observed in these cells. Our findings indicate that in cardiomyocytes, a nuclear pool of Cav2 participates in cellular functions that are independent of LTCC activity. They also indicate that a downregulation of nuclear Cav2 during cardiac hypertrophy promotes the activation of calpain-dependent hypertrophic pathways.
HostingRepositoryPRIDE
AnnounceDate2021-09-09
AnnouncementXMLSubmission_2021-09-08_17:17:11.443.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD016483
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterKatalin Barkovits
SpeciesList scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationListresidues isobaric at 113.084064 Da; Oxidation; Carbamidomethyl
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-11-27 07:58:12ID requested
12021-09-08 17:17:12announced
Publication List
Pickel S, Cruz-Garcia Y, Bandleon S, Barkovits K, Heindl C, V, ö, lker K, Abe, ß, er M, Pfeiffer K, Schaaf A, Marcus K, Eder-Negrin P, Kuhn M, Miranda-Laferte E, -Subunit of Voltage-Gated Calcium Channels Regulates Cardiomyocyte Hypertrophy. Front Cardiovasc Med, 8():704657(2021) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: L-type voltage-gated calcium channels
Cav-subunit
cardiac hypertrophy
calpain
cardiomyocytes
calpastatin
Contact List
Katalin Barkovits
contact affiliationRuhr-Universität Bochum Medizinisches Proteom-Center Raum 2.250 Gesundheitscampus 4 44801 Bochum Germany
contact emailkatalin.barkovits@rub.de
lab head
Katalin Barkovits
contact affiliationRuhr University Bochum
contact emailkatalin.barkovits@rub.de
dataset submitter
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