PXD016483 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The β2-subunit of voltage-gated calcium channels inhibits cardiomyocyte hypertrophy through a channel-independent mechanism. |
Description | L-type voltage-gated calcium channels (LTCCs) regulate crucial physiological processes in the heart. They are composed of the Cav1 pore-forming subunit and the accessory subunits Cav, Cav2 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 Cav2 downregulation enhances 1-adrenergic receptor agonist-induced cardiomyocyte hypertrophy in an LTCC-independent manner. We report that a pool of Cav2 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 Cav2 in cardiomyocytes inhibits in vitro-induced hypertrophy. Quantitative proteomic analyses showed that Cav2 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, Cav2-deficient cardiomyocytes had a two-fold increase in calpain activity as compared to control cells. Furthermore, inhibition of calpain activity in Cav2-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 Cav2 participates in cellular functions that are independent of LTCC activity. They also indicate that a downregulation of nuclear Cav2 during cardiac hypertrophy promotes the activation of calpain-dependent hypertrophic pathways. |
HostingRepository | PRIDE |
AnnounceDate | 2021-09-09 |
AnnouncementXML | Submission_2021-09-08_17:17:11.443.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD016483 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Katalin Barkovits |
SpeciesList | scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116; |
ModificationList | residues isobaric at 113.084064 Da; Oxidation; Carbamidomethyl |
Instrument | LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-11-27 07:58:12 | ID requested | |
⏵ 1 | 2021-09-08 17:17:12 | announced | |
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 affiliation | Ruhr-Universität Bochum Medizinisches Proteom-Center Raum 2.250 Gesundheitscampus 4 44801 Bochum Germany |
contact email | katalin.barkovits@rub.de |
lab head | |
Katalin Barkovits |
contact affiliation | Ruhr University Bochum |
contact email | katalin.barkovits@rub.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD016483
- Label: PRIDE project
- Name: The β2-subunit of voltage-gated calcium channels inhibits cardiomyocyte hypertrophy through a channel-independent mechanism.