肿瘤抑制因子eIF3e介导L型钙通道CaV1.2的钙依赖性内吞作用。
The tumor suppressor eIF3e mediates calcium-dependent internalization of the L-type calcium channel CaV1.2.
作者信息
Green Eric M, Barrett Curtis F, Bultynck Geert, Shamah Steven M, Dolmetsch Ricardo E
机构信息
Department of Neurobiology, Stanford University, 299 Campus Drive, Fairchild Research Building D227, Stanford, CA 94305, USA.
出版信息
Neuron. 2007 Aug 16;55(4):615-32. doi: 10.1016/j.neuron.2007.07.024.
Abstract
Voltage-gated calcium channels (VGCCs) convert electrical activity into calcium (Ca2+) signals that regulate cellular excitability, differentiation, and connectivity. The magnitude and kinetics of Ca2+ signals depend on the number of VGCCs at the plasma membrane, but little is known about the regulation of VGCC surface expression. We report that electrical activity causes internalization of the L-type Ca2+ channel (LTC) CaV1.2 and that this is mediated by binding to the tumor suppressor eIF3e/Int6 (eukaryotic initiation factor 3 subunit e). Using total internal reflection microscopy, we identify a population of CaV1.2 containing endosomes whose rapid trafficking is strongly regulated by Ca2+. We define a domain in the II-III loop of CaV1.2 that binds eIF3e and is essential for the activity dependence of both channel internalization and endosomal trafficking. These findings provide a mechanism for activity-dependent internalization and trafficking of CaV1.2 and provide a tantalizing link between Ca2+ homeostasis and a mammalian oncogene.
摘要
电压门控钙通道（VGCCs）将电活动转化为钙（Ca2+）信号，这些信号调节细胞兴奋性、分化和连接性。Ca2+信号的幅度和动力学取决于质膜上VGCCs的数量，但关于VGCCs表面表达的调节知之甚少。我们报告电活动导致L型钙通道（LTC）CaV1.2内化，这是通过与肿瘤抑制因子eIF3e/Int6（真核起始因子3亚基e）结合介导的。使用全内反射显微镜，我们鉴定出一群含有内体的CaV1.2，其快速运输受到Ca2+的强烈调节。我们在CaV1.2的II-III环中定义了一个与eIF3e结合的结构域，该结构域对于通道内化和内体运输的活性依赖性至关重要。这些发现提供了一种CaV1.2活性依赖性内化和运输的机制，并在Ca2+稳态与哺乳动物癌基因之间提供了一个诱人的联系。
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