| Autor: |
Ravindran, Arippa, Qi Zong Lao, Harry, Jo Beth, Abrahimi, Parwiz, Kobrinsky, Evgeny, Soldatov, Nikolai M. |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 6/10/2008, Vol. 105 Issue 23, p8154-8159, 6p, 6 Graphs |
| Abstrakt: |
It is generally accepted that to generate calcium currents in response to depolarization, Cav1.2 calcium channels require association of the pore-forming α1C subunit with accessory Cavβ and α2δ subunits. A single calmodulin (CaM) molecule is tethered to the C-terminal α1C-LA/IQ region and mediates Ca2+-dependent inactivation of the channel. Cavβ subunits are stably associated with the α1C-interaction domain site of the cytoplasmic linker between internal repeats I and II and also interact dynamically, in a Ca2+-dependent manner, with the α1C-IQ region. Here, we describe a surprising discovery that coexpression of exogenous CaM (CaMex) with α1C/α2δ in COS1 cells in the absence of Cavβ subunits stimulates the plasma membrane targeting of α1C, facilitates calcium channel gating, and supports Ca2+-dependent inactivation. Neither real-time PCR with primers complementary to monkey Cavβ subunits nor coimmunoprecipitation analysis with exogenous α1C revealed an induction of endogenous Ca!p subunits that could be linked to the effect of CaMex. Coexpression of a calcium-insensitive CaM mutant CaM1234 also facilitated gating of Cavβ-free Cav1.2 channels but did not support Ca2+-dependent inactivation. Our results show there is a functional matchup between CaMex and Cavβ subunits that, in the absence of Cavβ, renders Ca2+ channel gating facilitated by CaM molecules other than the one tethered to LA/IQ to support Ca2+-dependent inactivation. Thus, coexpression of CaMex creates conditions when the channel gating, voltage- and Ca2+-dependent inactivation, and plasma-membrane targeting occur in the absence of Cavβ. We suggest that CaMex affects specific Cavβ-free conformations of the channel that are not available to endogenous CaM. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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