PXD057841-1

PXD057841 is an original dataset announced via ProteomeXchange.

Title	Tripartite interactions of PKA catalytic subunit and C-terminal domains of cardiac Ca2+ channel may modulate its β-adrenergic regulation
Description	The β-adrenergic augmentation of cardiac contraction, by increasing the conductivity of L-type voltage-gated CaV1.2 channels, is of great physiological and pathophysiological importance. Stimulation of β-adrenergic receptors (βAR) activates protein kinase A (PKA) through separation of regulatory (PKAR) from catalytic (PKAC) subunits. Free PKAC phosphorylates the inhibitory protein Rad, leading to increased Ca2+ influx. In cardiomyocytes, the core subunit of CaV1.2, CaV1.2α1, exists in two forms: full-length or truncated (lacking the distal C-terminus (dCT)). Signaling efficiency is believed to emanate from protein interactions within multimolecular complexes, such as anchoring PKA (via PKAR) to CaV1.2α1 by A-kinase anchoring proteins (AKAPs). However, AKAPs are inessential for βAR regulation of CaV1.2 in heterologous models, and their role in cardiomyocytes also remains unclear. Results: We show that PKAC interacts with CaV1.2α1 in heart and a heterologous model, independently of Rad, PKAR or AKAPs. Studies with peptide array assays and purified recombinant proteins demonstrate direct binding of PKAC to two domains in CaV1.2α1-CT: the proximal and distal C-terminal regulatory domains (PCRD and DCRD), which also interact with each other. Data indicate both partial competition and possible simultaneous interaction of PCRD and DCRD with PKAC. The βAR regulation of CaV1.2α1 lacking dCT (which harbors DCRD) was preserved, but subtly altered, in a heterologous model, the Xenopus oocyte. Conclusions: We discover direct interactions between PKAC and two domains in CaV1.2α1. We propose that these tripartite interactions, if present in vivo, may participate in organizing the multimolecular signaling complex and fine-tuning the βAR effect in cardiomyocytes.
HostingRepository	PRIDE
AnnounceDate	2024-11-22
AnnouncementXML	Submission_2024-11-22_01:04:20.922.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD057841
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Claudia Fecher-Trost
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-13 05:35:22	ID requested
⏵ 1	2024-11-22 01:04:21	announced

10.6019/PXD057841;

submitter keyword: calcium channel

protein‐protein interaction

adrenergic regulation

cardiac

protein kinase A (PKA)

heterologous expression

Nathan Dascal
contact affiliation	Nathan Dascal, Ph.D. Tel Aviv University School of Medicine ISRAEL dascaln@tauex.tau.ac.il
contact email	dascaln@tauex.tau.ac.il
lab head
Claudia Fecher-Trost
contact affiliation	PZMS
contact email	claudia.fecher-trost@uks.eu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057841
     1. Label: PRIDE project
     2. Name: Tripartite interactions of PKA catalytic subunit and C-terminal domains of cardiac Ca2+ channel may modulate its β-adrenergic regulation