| Autor: |
Merav Mor, Ofer Beharier, David I Cook, Craig R Campbell, Levi A Gheber, Amos Katz, Arie Moran, Yoram Etzion |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Metallomics. |
| ISSN: |
1756-591X |
| Popis: |
ZnT1 is a major zinc transporter that regulates cellular zinc homeostasis. We have previously shown that ZnT1 have additional functions which 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 function. 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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