PXD016483

PXD016483 is an original dataset announced via ProteomeXchange.

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 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.
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

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-27 07:58:12	ID requested
⏵ 1	2021-09-08 17:17:12	announced

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]

curator keyword: Biological

submitter keyword: L-type voltage-gated calcium channels

Cav-subunit

cardiac hypertrophy

calpain

cardiomyocytes

calpastatin

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

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PRIDE project URI

• PRIDE
  1. PXD016483
     1. Label: PRIDE project
     2. Name: The β2-subunit of voltage-gated calcium channels inhibits cardiomyocyte hypertrophy through a channel-independent mechanism.