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首页> 外文期刊>Cellular Signalling >Analysis of the Rem2 - voltage dependant calcium channel beta subunit interaction and Rem2 interaction with phosphorylated phosphatidylinositide lipids
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Analysis of the Rem2 - voltage dependant calcium channel beta subunit interaction and Rem2 interaction with phosphorylated phosphatidylinositide lipids

机译：Rem2-电压依赖性钙通道β亚基相互作用和Rem2与磷酸化磷脂酰肌醇脂质的相互作用的分析

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摘要

Voltage dependant calcium channels (VDCC) play a critical role in coupling electrical excitability to important physiological events such as secretion by neuronal and endocrine cells. Rem2, a GTPase restricted to neuroendocrine cell types, regulates VDCC activity by a mechanism that involves interaction with the VDCC beta subunit (Cav beta). Mapping studies reveal that Rem2 binds to the guanylate kinase domain (GK) of the Cav beta subunit that also contains the high affinity binding site for the pore forming and voltage sensing VDCC a subunit (Ca-v beta) interaction domain (AID). Moreover, fine mapping indicates that Rem2 binds to the GK domain in a region distinct from the AID interaction site, and competitive inhibition studies reveal that Rem2 does not disrupt Ca-v alpha - Ca-v beta binding. Instead, the Cav beta subunit appears to serve a scaffolding function, simultaneously binding both Rem2 and AID. Previous studies have found that in addition to Ca-v beta binding, Rem2 must be localized to the plasma membrane to inhibit VDCC function. Plasma membrane localization requires the C-tenninus of Rem2 and binding studies indicate that this domain directs phosphorylated phosphatidylinositide (PIP) lipids association. Plasma membrane localization may provide a unique point of regulation since the ability of Rem2 to bind PIP lipids is inhibited by the phosphoserine dependant binding of 14-3-3 proteins. Thus, in addition to Ca-v beta binding, VDCC blockade by Rem2 is likely to be controlled by both the localized concentration of membrane PIP lipids and direct 14-3-3 binding to the Rem2 C-terminus. (C) 2007 Elsevier Inc. All rights reserved.
机译：电压依赖性钙通道（VDCC）在将电兴奋性与重要的生理事件（例如神经元和内分泌细胞的分泌）耦合中起着关键作用。 Rem2是一种仅限于神经内分泌细胞类型的GTP酶，它通过涉及与VDCC beta亚基（Cav beta）相互作用的机制调节VDCC活性。映射研究表明，Rem2结合到Cav beta亚基的鸟苷酸激酶结构域（GK），该结构域还包含用于孔形成和电压感应VDCC亚基（Ca-v beta）相互作用域（AID）的高亲和力结合位点。此外，精细定位表明Rem2在与AID相互作用位点不同的区域与GK结构域结合，竞争抑制研究表明Rem2不会破坏Ca-v alpha-Ca-v beta结合。相反，Cav beta亚基似乎具有脚手架功能，同时结合Rem2和AID。先前的研究发现，除了Ca-vβ结合外，Rem2还必须位于质膜上才能抑制VDCC功能。质膜定位需要Rem2的C末端，结合研究表明该结构域指导磷酸化磷脂酰肌醇（PIP）脂质的缔合。由于Rem2结合PIP脂质的能力被14-3-3蛋白的磷酸丝氨酸依赖性结合所抑制，因此质膜定位可能会提供独特的调控点。因此，除了Ca-vβ结合之外，Rem2对VDCC的阻断还可能受膜PIP脂质的局部浓度和直接与Rem2 C末端的14-3-3结合的控制。 （C）2007 Elsevier Inc.保留所有权利。

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