Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Erik Renström

Erik Renström

Vice-chancellor

Erik Renström

Palmitoylation of Ca2+ channel subunit CaVβ2a induces pancreatic beta-cell toxicity via Ca2+ overload

Author

  • Abdulla S. Kazim
  • Petter Storm
  • Enming Zhang
  • Erik Renström

Summary, in English

High blood glucose triggers the release of insulin from pancreatic beta cells, but if chronic, causes cellular stress, partly due to impaired Ca2+ homeostasis. Ca2+ influx is controlled by voltage-gated calcium channels (CaV) and high density of CaV in the plasma membrane could lead to Ca2+ overload. Trafficking of the pore-forming CaVα1 subunit to the plasma membrane is regulated by auxiliary subunits, such as the CaVβ2a subunit. This study investigates, using Ca2+ imaging and immunohistochemistry, the role of palmitoylation of CaVβ2a in maintaining Ca2+ homeostasis and beta cell function. RNA sequencing data showed that gene expression of human CACNB2, in particular CACNB2A (CaVβ2a), is highest in islets when compared to other tissues. Since CaVβ2a can be regulated through palmitoylation of its two cysteines, CaVβ2a and its mutant form were overexpressed in pancreatic beta cells. Palmitoylated CaVβ2a tethered to the plasma membrane and colocalized with CaV1.2 while the mutant form remained in the cytosol. Interestingly, CaVβ2a overexpression raised basal intracellular Ca2+ and increased beta cell apoptosis. Our study shows that palmitoylation of CaVβ2a is necessary for CaVα1 trafficking to the plasma membrane. However, excessive number of palmitoylated CaVβ2a leads to Ca2+ overload and beta cell death.

Department/s

  • Diabetes - Islet Patophysiology
  • Glucose Transport and Protein Trafficking
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2017-07-21

Language

English

Pages

740-746

Publication/Series

Biochemical and Biophysical Research Communications

Volume

491

Issue

3

Document type

Journal article

Publisher

Elsevier

Topic

  • Medicinal Chemistry
  • Endocrinology and Diabetes

Keywords

  • Apoptosis
  • Beta cells
  • Caβ
  • Palmitoylation

Status

Published

Research group

  • Diabetes - Islet Patophysiology
  • Glucose Transport and Protein Trafficking

ISBN/ISSN/Other

  • ISSN: 0006-291X