PXD044630

PXD044630 is an original dataset announced via ProteomeXchange.

Title	Quality control at the cell surface prevents accumulation of damaged L-type CaV1.2 calcium channels
Description	Defective ion channel turnover and clearance of damaged proteins are associated with aging and neurodegeneration. The L-type CaV1.2 voltage-gated calcium channel mediate depolarization-induced calcium signals in heart and brain. Here, we determined the interaction surface between the L-type calcium channel CaVβ subunit and actin using cross-linking mass spectrometry and protein-protein docking, and uncovered a role in replenishing damaged CaV1.2 channels. Computational and in vitro mutagenesis identified hotspots in CaVβ that decrease its affinity for actin but not for CaV1.2. Coexpression of an actin-association-deficient CaVβ mutant with the CaV1.2 channel downregulated current amplitudes with a concomitant reduction in the number of functionally available channels. Neither alterations in the single-channel properties nor changes in the total number of channels at the cell surface were found, indicating that current inhibition resulted from a build-up of conduction-defective channels. Our findings established CaVβ–actin interaction as a key player for selective monitoring and clearing corrupted CaV proteins to ensure the maintenance of a functional pool of channels and proper calcium signal transduction. The CaVβ–actin molecular model introduces a potentially druggable protein-protein interface to intervene CaV-mediated signaling processes.
HostingRepository	PRIDE
AnnounceDate	2024-02-16
AnnouncementXML	Submission_2024-02-15_23:45:09.223.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Beatrix Santiago-Schuebel
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Oryctolagus cuniculus (Rabbit); NCBI TaxID: 9986;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-18 08:33:15	ID requested
⏵ 1	2024-02-15 23:45:09	announced

Dataset with its publication pending

submitter keyword: calcium channel β-subunit, hotspots, cross-linking mass spectrometry, protein-protein docking, CaV1.2 surface expression, actin filaments

Beatrix Santiago
contact affiliation	Forschungszentrum Jülich, Germany
contact email	b.santiago-schuebel@fz-juelich.de
lab head
Beatrix Santiago-Schuebel
contact affiliation	Forschungszentrum Juelich, ZEA-3
contact email	b.santiago-schuebel@fz-juelich.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044630
     1. Label: PRIDE project
     2. Name: Quality control at the cell surface prevents accumulation of damaged L-type CaV1.2 calcium channels