Apolipoprotein CIII hyperactivates β cell CaV1 channels through SR-BI/β1 integrin-dependent coactivation of PKA and Src

Yue Shi, Guang Yang, Jia Yu, Lina Yu, Ruth Westenbroek, William A. Catterall, Lisa Juntti-Berggren, Per Olof Berggren, Shao Nian Yang

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Apolipoprotein CIII (ApoCIII) not only serves as an inhibitor of triglyceride hydrolysis but also participates in diabetes-related pathological events such as hyperactivation of voltage-gated Ca(2+) (CaV) channels in the pancreatic β cell. However, nothing is known about the molecular mechanisms whereby ApoCIII hyperactivates β cell CaV channels. We now demonstrate that ApoCIII increased CaV1 channel open probability and density. ApoCIII enhanced whole-cell Ca(2+) currents and the CaV1 channel blocker nimodipine completely abrogated this enhancement. The effect of ApoCIII was not influenced by individual inhibition of PKA, PKC, or Src. However, combined inhibition of PKA, PKC, and Src counteracted the effect of ApoCIII, similar results obtained by coinhibition of PKA and Src. Moreover, knockdown of β1 integrin or scavenger receptor class B type I (SR-BI) prevented ApoCIII from hyperactivating β cell CaV channels. These data reveal that ApoCIII hyperactivates β cell CaV1 channels through SR-BI/β1 integrin-dependent coactivation of PKA and Src.

Original languageEnglish (US)
Pages (from-to)1289-1303
Number of pages15
JournalCellular and Molecular Life Sciences
Volume71
Issue number7
DOIs
StatePublished - Apr 1 2014

Keywords

  • Ca channel
  • Integrin
  • Pancreatic β cell
  • Protein kinase
  • Scavenger receptor

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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    Shi, Y., Yang, G., Yu, J., Yu, L., Westenbroek, R., Catterall, W. A., Juntti-Berggren, L., Berggren, P. O., & Yang, S. N. (2014). Apolipoprotein CIII hyperactivates β cell CaV1 channels through SR-BI/β1 integrin-dependent coactivation of PKA and Src. Cellular and Molecular Life Sciences, 71(7), 1289-1303. https://doi.org/10.1007/s00018-013-1442-x