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

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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
Pages (from-to)1289-1303
Number of pages15
JournalCellular and molecular life sciences : CMLS
Volume71
Issue number7
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Apolipoprotein C-III
CD36 Antigens
Integrins
Nimodipine
Medical problems
Hydrolysis
Triglycerides

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Apolipoprotein CIII hyperactivates β cell CaV1 channels through SR-BI/β1 integrin-dependent coactivation of PKA and Src. / Shi, Yue; Yang, Guang; Yu, Jia; Yu, Lina; Westenbroek, Ruth; Catterall, William A.; Juntti-Berggren, Lisa; Berggren, Per Olof; Yang, Shao Nian.

In: Cellular and molecular life sciences : CMLS, Vol. 71, No. 7, 01.01.2014, p. 1289-1303.

Research output: Contribution to journalArticle

Shi, Y, Yang, G, Yu, J, Yu, L, Westenbroek, R, Catterall, WA, Juntti-Berggren, L, Berggren, PO & Yang, SN 2014, 'Apolipoprotein CIII hyperactivates β cell CaV1 channels through SR-BI/β1 integrin-dependent coactivation of PKA and Src.', Cellular and molecular life sciences : CMLS, vol. 71, no. 7, pp. 1289-1303. https://doi.org/10.1007/s00018-013-1442-x
Shi, Yue ; Yang, Guang ; Yu, Jia ; Yu, Lina ; Westenbroek, Ruth ; Catterall, William A. ; Juntti-Berggren, Lisa ; Berggren, Per Olof ; Yang, Shao Nian. / Apolipoprotein CIII hyperactivates β cell CaV1 channels through SR-BI/β1 integrin-dependent coactivation of PKA and Src. In: Cellular and molecular life sciences : CMLS. 2014 ; Vol. 71, No. 7. pp. 1289-1303.
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