Apolipoprotein CIII hyperactivates β cell CaV1 channels through SR-BI/β1 integrin-dependent coactivation of PKA and Src.
Apolipoprotein CIII hyperactivates β cell CaV1 channels through SR-BI/β1 integrin-dependent coactivation of PKA and Src.
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DOI：
10.1007/s00018-013-1442-x
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发表时间：
2014-04
影响因子：
8
通讯作者：
Yang, Shao-Nian
中科院分区：
文献类型：
--
作者：
Shi, Yue;Yang, Guang;Yu, Jia;Yu, Lina;Westenbroek, Ruth;Catterall, William A.;Juntti-Berggren, Lisa;Berggren, Per-Olof;Yang, Shao-Nian
载脂蛋白CIII不仅是甘油三酯水解酶的抑制因子，还参与了糖尿病相关的病理事件，如胰腺β细胞电压门控钙通道的过度激活。然而，关于载脂蛋白CⅢ激活β细胞Cav通道的分子机制尚不清楚。我们现在证明APOCIII增加了CaV1通道的开放概率和密度。APOCIII增强全细胞钙电流，CaV1通道阻断剂尼莫地平完全阻断这种增强作用。APOCIII的作用不受单独抑制PKA、PKC或Src的影响。然而，联合抑制PKA、PKC和Src可抵消APOCIII的作用，这一结果与联合抑制PKA和Src的结果相似。此外，敲除β1整合素或清道夫受体BI型(SR-BI)可阻止APOCIII过度激活β细胞的Cav通道。这些结果表明，APOCIII通过依赖SR-BI/β-1整合素共激活PKA和β来过度激活CAV_1通道。
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.
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影响因子：
9.8
作者：
Atzmon, Gil;Rincon, Marielisa;Schechter, Clyde B;Shuldiner, Alan R;Lipton, Richard B;Bergman, Aviv;Barzilai, Nir
通讯作者：
Barzilai, Nir
影响因子：
7.7
作者：
Mukai E;Fujimoto S;Sato H;Oneyama C;Kominato R;Sato Y;Sasaki M;Nishi Y;Okada M;Inagaki N
通讯作者：
Inagaki N
DOI：
10.1073/pnas.1019553108
发表时间：
2011-06-28
影响因子：
11.1
作者：
Holmberg, Rebecka;Refai, Essam;Juntti-Berggren, Lisa
通讯作者：
Juntti-Berggren, Lisa
DOI：
10.1016/j.biocel.2005.01.005
发表时间：
2005-06-01
影响因子：
4
作者：
Huard, K;Bourgeois, P;Brissette, L
通讯作者：
Brissette, L
影响因子：
37.8
作者：
Kawakami, A;Aikawa, M;Sacks, FM
通讯作者：
Sacks, FM