Cellular and Molecular Life Sciences

, Volume 71, Issue 7, pp 1289–1303

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 Article

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 Ca2+ (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 Ca2+ 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.

Keywords

Ca2+ channel Integrin Pancreatic β cell Protein kinase Scavenger receptor 

Abbreviations

ApoCIII

Apolipoprotein CIII

CaV

Voltage-gated Ca2+

SR-BI

Scavenger receptor class B type I

Supplementary material

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Supplementary material (DOC 42 kb)

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Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Yue Shi
    • 1
  • Guang Yang
    • 1
    • 2
  • Jia Yu
    • 1
  • Lina Yu
    • 1
  • Ruth Westenbroek
    • 3
  • William A. Catterall
    • 3
  • Lisa Juntti-Berggren
    • 1
  • Per-Olof Berggren
    • 1
  • Shao-Nian Yang
    • 1
  1. 1.The Rolf Luft Research Center for Diabetes and EndocrinologyKarolinska InstitutetStockholmSweden
  2. 2.Jilin Academy of Traditional Chinese MedicineChangchunChina
  3. 3.Department of Pharmacology, School of MedicineUniversity of WashingtonSeattleUSA

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