Chemico-genetic identification of drebrin as a regulator of calcium responses.

Chemico-genetic identification of drebrin as a regulator of calcium responses.
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DOI:
10.1016/j.biocel.2009.11.019
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发表时间:
2010-02
影响因子:
4
通讯作者:
August, Avery
August, Avery
中科院分区:
生物学2区
文献类型:
--
作者:
Mercer, Jason C.;Qi, Qian;Mottram, Laurie F.;Law, Mankit;Bruce, Danny;Iyer, Archana;Morales, J. Luis;Yamazaki, Hiroyuki;Shirao, Tomoaki;Peterson, Blake R.;August, Avery

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钙库操作的钙通道是质膜钙通道,通过耗尽细胞内钙库而激活,导致细胞内钙离子浓度升高,在某些类型的细胞中可维持较长时间。细胞内钙离子浓度的升高是激活许多细胞过程的信号,然而,对这些通道的调节知之甚少。我们已经确定了免疫抑制化合物BTP的特征,它阻止商店操作的通道介导的钙内流进入细胞。使用亲和纯化方案来确定BTP的潜在靶点,我们鉴定了肌动蛋白重组蛋白Drebrin,并证明了Drebrin蛋白表达的缺失阻止了商店操作的通道介导的钙内流,与BTP处理类似。BTP还可以阻断由Drebrin诱导的肌动蛋白重排。虽然肌动蛋白的细胞骨架重组与钙离子通道调控有关,但对参与这一过程的肌动蛋白结合蛋白以及肌动蛋白如何调控钙通道功能知之甚少。Drebrin作为这一过程的中介体的发现将为肌动蛋白重排和Tore操作的通道介导的钙内流之间的相互作用提供新的见解。
Store-operated calcium channels are plasma membrane Ca2+ channels that are activated by depletion of intracellular Ca2+ stores, resulting in an increase in intracellular Ca2+ concentration, which is maintained for prolonged periods in some cell types. Increases in intracellular Ca2+ concentration serve as signals that activate a number of cellular processes, however, little is known about the regulation of these channels. We have characterized the immuno-suppressant compound BTP, which blocks store-operated channel mediated calcium influx into cells. Using an affinity purification scheme to identify potential targets of BTP, we identified the actin reorganizing protein, drebrin, and demonstrated that loss of drebrin protein expression prevents store-operated channel mediated Ca2+ entry, similar to BTP treatment. BTP also blocks actin rearrangements induced by drebrin. While actin cytoskeletal reorganization has been implicated in store-operated calcium channel regulation, little is known about actin binding proteins that are involved in this process, or how actin regulates channel function. The identification of drebrin as a mediator of this process should provide new insight into the interaction between actin rearrangement and tore-operated channel mediated calcium influx.
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