Rem GTPase interacts with the proximal CaV1.2 C-terminus and modulates calcium-dependent channel inactivation.
Rem GTPase interacts with the proximal CaV1.2 C-terminus and modulates calcium-dependent channel inactivation.
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DOI：
10.4161/chan.4.3.11867
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发表时间：
2010-05
期刊：
影响因子：
--
通讯作者：
Andres DA
中科院分区：
文献类型：
--
作者：
Pang C;Crump SM;Jin L;Correll RN;Finlin BS;Satin J;Andres DA
The Rem, Rem2, Rad, and Gem/Kir (RGK) GTPases, comprise a subfamily of small Ras-related GTP-binding proteins, and have been shown to potently inhibit high voltage-activated Ca2+ channel current following overexpression. Although the molecular mechanisms underlying RGK-mediated Ca2+ channel regulation remains controversial, recent studies suggest that RGK proteins inhibit Ca2+ channel currents at the plasma membrane in part by interactions with accessory channel β subunits. In this paper, we extend our understanding of the molecular determinants required for RGK-mediated channel regulation by demonstrating a direct interaction between Rem and the proximal C-terminus of CaV1.2 (PCT), including the CB/IQ domain known to contribute to Ca2+/calmodulin (CaM)-mediated channel regulation. The Rem2 and Rad GTPases display similar patterns of PCT binding, suggesting that the CaV1.2 C-terminus represents a common binding partner for all RGK proteins. In vitro Rem:PCT binding is disrupted by Ca2+/CaM, and this effect is not due to Ca2+/CaM binding to the Rem C-terminus. In addition, co-overexpression of CaM partially relieves Rem-mediated L-type Ca2+ channel inhibition and slows the kinetics of Ca2+-dependent channel inactivation. Taken together, these results suggest that the association of Rem with the PCT represents a crucial molecular determinant in RGK-mediated Ca2+ channel regulation and that the physiological function of the RGK GTPases must be reevaluated. Rather than serving as endogenous inhibitors of Ca2+ channel activity, these studies indicate that RGK proteins may play a more nuanced role, regulating Ca2+ currents via modulation of Ca2+/CaM-mediated channel inactivation kinetics.
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DOI：
10.1073/pnas.262372999
发表时间：
2002-12-24
影响因子：
11.1
作者：
Alseikhan, BA;DeMaria, CD;Yue, DT
通讯作者：
Yue, DT
影响因子：
64.8
作者：
Béguin, P;Nagashima, K;Seino, S
通讯作者：
Seino, S
DOI：
10.1073/pnas.91.26.12448
发表时间：
1994-12-20
影响因子：
11.1
作者：
COHEN, L;MOHR, R;WITTE, O
通讯作者：
WITTE, O
DOI：
10.1073/pnas.88.23.10778
发表时间：
1991-12-01
影响因子：
11.1
作者：
DEJONGH, KS;WARNER, C;CATTERALL, WA
通讯作者：
CATTERALL, WA
影响因子：
4.8
作者：
Correll, Robert N.;Pang, Chunyan;Andres, Douglas A.
通讯作者：
Andres, Douglas A.