Please use this identifier to cite or link to this item: doi:10.22028/D291-42630
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Title: Cavβ3 Regulates Ca2+ Signaling and Insulin Expression in Pancreatic β-Cells in a Cell-Autonomous Manner
Author(s): Becker, Alexander
Wardas, Barbara
Salah, Houssein
Amini, Maryam
Fecher-Trost, Claudia
Sen, Qiao
Martus, Damian
Beck, Andreas
Philipp, Stephan E.
Flockerzi, Veit
Belkacemi, Anouar
Language: English
Title: Diabetes
Volume: 70
Issue: 11
Pages: 2532-2544
Publisher/Platform: American Diabetes Association
Year of Publication: 2021
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Voltage-gated Ca2+ (Cav) channels consist of a pore-forming Cava1 subunit and auxiliary Cava2-d and Cavb subunits. In fibroblasts, Cavb3, independent of its role as a Cav subunit, reduces the sensitivity to low concentrations of inositol-1,4,5-trisphosphate (IP3). Similarly, Cavb3 could affect cytosolic calcium concentration ([Ca2+]) in pancreatic b-cells. In this study, we deleted the Cavb3-encoding gene Cacnb3 in insulin-secreting rat b-(Ins-1) cells using CRISPR/Cas9. These cells were used as controls to investigate the role of Cavb3 on Ca2+ signaling, glucoseinduced insulin secretion (GIIS), Cav channel activity, and gene expression in wild-type cells in which Cavb3 and the IP3 receptor were coimmunoprecipitated. Transcript and protein profiling revealed significantly increased levels of insulin transcription factor Mafa, CaMKIV, proprotein convertase subtilisin/kexin type-1, and nitric oxide synthase-1 in Cavb3-knockout cells. In the absence of Cavb3, Cav currents were not altered. In contrast, CREB activity, the amount of MAFA protein and GIIS, the extent of IP3-dependent Ca2+ release and the frequency of Ca2+ oscillations were increased. These processes were decreased by the Cavb3 protein in a concentration-dependent manner. Our study shows that Cavb3 interacts with the IP3 receptor in isolated b-cells, controls IP3-dependent Ca2+-signaling independently of Cav channel functions, and thereby regulates insulin expression and its glucose-dependent release in a cell-autonomous manner.
DOI of the first publication: 10.2337/db21-0078
URL of the first publication: https://doi.org/10.2337/db21-0078
Link to this record: urn:nbn:de:bsz:291--ds-426309
hdl:20.500.11880/38233
http://dx.doi.org/10.22028/D291-42630
ISSN: 0012-1797
Date of registration: 12-Aug-2024
Description of the related object: supplementary material
Related object: https://ndownloader.figstatic.com/files/29148480
Faculty: M - Medizinische Fakultät
Department: M - Experimentelle und Klinische Pharmakologie und Toxikologie
Professorship: M - Prof. Dr. Veit Flockerzi
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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