ZnT1 induces a crosstalk between T-type and L-type calcium channels through interactions with Raf-1 kinase and the calcium channel β2 subunit.,Metallomics

当前位置： X-MOL 学术 › Metallomics › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

ZnT1 induces a crosstalk between T-type and L-type calcium channels through interactions with Raf-1 kinase and the calcium channel β2 subunit.
Metallomics ( IF 3.4 ) Pub Date : 2023-06-01 , DOI: 10.1093/mtomcs/mfad031
Merav Mor ₁ , Ofer Beharier ₁ , David I Cook ₂ , Craig R Campbell ₂ , Levi A Gheber ₃ , Amos Katz ₄ , Arie Moran _{1,

2} , Yoram Etzion _{5,

6}

Affiliation

ZnT1 is a major zinc transporter that regulates cellular zinc homeostasis. We have previously shown that ZnT1 has additional functions that are independent of its activity as a Zn2+ extruder. These include inhibition of the L-type calcium channel (LTCC) through interaction with the auxiliary β-subunit of the LTCC and activation of the Raf-ERK signaling leading to augmented activity of the T-type calcium channel (TTCC). Our findings indicate that ZnT1 increases TTCC activity by enhancing the trafficking of the channel to the plasma membrane. LTCC and TTCC are co-expressed in many tissues and have different functions in a variety of tissues. In the current work, we investigated the effect of the voltage-gated calcium channel (VGCC) β-subunit and ZnT1 on the crosstalk between LTCC and TTCC and their functions. Our results indicate that the β-subunit inhibits the ZnT1-induced augmentation of TTCC function. This inhibition correlates with the VGCC β-subunit-dependent reduction in ZnT1-induced activation of Ras-ERK signaling. The effect of ZnT1 is specific, as the presence of the β-subunit did not change the effect of endothelin-1 (ET-1) on TTCC surface expression. These findings document a novel regulatory function of ZnT1 serving as a mediator in the crosstalk between TTCC and LTCC. Overall, we demonstrate that ZnT1 binds and regulates the activity of the β-subunit of VGCC and Raf-1 kinase and modulates surface expression of the LTCC and TTCC catalytic subunits, consequently modulating the activity of these channels.

更新日期：2023-05-16

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>