Center for Molecular Immunology & Infectious Disease, Department of Veterinary & Biomedical Science, The Pennsylvania State University, University Park, PA 16802, USA.
Int J Biochem Cell Biol. 2010 Feb;42(2):337-45. doi: 10.1016/j.biocel.2009.11.019. Epub 2009 Dec 3.
Store-operated calcium channels are plasma membrane Ca(2+) channels that are activated by depletion of intracellular Ca(2+) stores, resulting in an increase in intracellular Ca(2+) concentration, which is maintained for prolonged periods in some cell types. Increases in intracellular Ca(2+) 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 Ca(2+) 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 store-operated channel mediated calcium influx.
钙库操纵型钙通道是质膜 Ca(2+)通道，其可被细胞内 Ca(2+)储存耗竭激活，导致细胞内 Ca(2+)浓度增加，在某些细胞类型中，该浓度的增加会维持较长时间。细胞内 Ca(2+)浓度的增加可作为激活多种细胞过程的信号，然而，这些通道的调节机制却知之甚少。我们已经对免疫抑制剂 BTP 进行了表征，BTP 可阻断钙库操纵型通道介导的细胞内 Ca(2+)内流。通过采用亲和纯化方案来鉴定 BTP 的潜在靶标，我们鉴定出了肌动蛋白重排蛋白 drebrin，并证实了丧失 drebrin 蛋白表达可阻止钙库操纵型通道介导的 Ca(2+)内流，其作用类似于 BTP 处理。BTP 还可阻断 drebrin 诱导的肌动蛋白重排。尽管肌动蛋白细胞骨架重排与钙库操纵型钙通道的调节有关，但人们对此过程中涉及的肌动蛋白结合蛋白知之甚少，也不清楚肌动蛋白如何调节通道功能。将 drebrin 鉴定为该过程的介质，应能深入了解肌动蛋白重排与钙库操纵型通道介导的 Ca(2+)内流之间的相互作用。
