Ca2+ and calmodulin regulate the binding of filamin A to actin filaments
Ca2+ and calmodulin regulate the binding of filamin A to actin filaments
复制标题
DOI：
10.1074/jbc.m502203200
复制
发表时间：
2005-09-16
影响因子：
4.8
通讯作者：
Szymanski, PT
中科院分区：
文献类型：
--
作者：
Nakamura, F;Hartwig, JH;Szymanski, PT
细丝蛋白 A (FLNa) 在细胞内将肌动蛋白丝 (F-actin) 交联成三维凝胶，将 F-肌动蛋白附着到膜蛋白上，是收集大量不同蛋白质的支架。我们报道 Ca2+-钙调蛋白结合 FLNa 的肌动蛋白结合域 (ABD)，并将 FLNa 与 F-肌动蛋白解离，从而溶解 (FLNaF)-F-.-肌动蛋白凝胶。 FLNa ABD 具有两个由接头分隔的钙调蛋白同源结构域（CH1 和 CH2）。在缺乏 F-肌动蛋白的情况下，重组 CH1 但 FLNa 及其 ABD 均不结合 Ca2+-钙调蛋白。扩展重组 CH1 以包含带负电荷的区域接头结构域，使其与全长 FLNa 一样，无法结合 Ca2+-钙调蛋白。然而，只要存在 CH2 结构域，Ca2+-钙调蛋白就会将 FLNa ABD 与 F-肌动蛋白解离。这些发现确定了直接调节 FLNa 的第一个证据，暗示了 Ca2+-钙调蛋白选择性靶向 (FLNaF)-F-.-肌动蛋白复合物的机制。
Filamin A (FLNa) cross-links actin filaments (F-actin) into three-dimensional gels in cells, attaches F-actin to membrane proteins, and is a scaffold that collects numerous and diverse proteins. We report that Ca2+-calmodulin binds the actin-binding domain (ABD) of FLNa and dissociates FLNa from F- actin, thereby dissolving (FLNaF)-F-.-actin gels. The FLNa ABD has two calponin homology domains (CH1 and CH2) separated by a linker. Recombinant CH1 but neither FLNa nor its ABD binds Ca2+-calmodulin in the absence of F- actin. Extending recombinant CH1 to include the negatively charged region linker domain makes it, like full-length FLNa, unable to bind Ca2+-calmodulin. Ca2+-calmodulin does, however, dissociate the FLNa ABD from F- actin provided that the CH2 domain is present. These findings identify the first evidence for direct regulation of FLNa, implicating amechanism whereby Ca2+-calmodulin selectively targets the (FLNaF)-F-.-actin complex.