Subcellular Localization of Talin Is Regulated by Inter-domain Interactions
Subcellular Localization of Talin Is Regulated by Inter-domain Interactions
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DOI：
10.1074/jbc.m112.341214
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发表时间：
2012-04-20
影响因子：
4.8
通讯作者：
Ginsberg, Mark H.
中科院分区：
文献类型：
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作者：
Banno, Asoka;Goult, Benjamin T.;Ginsberg, Mark H.
Talin 由头 (THD) 和杆结构域组成，在多种物种（包括大多数后生动物和盘基网柄菌）的细胞粘附事件中发挥着重要作用。 Talin 在细胞质中含量丰富；然而，它通过与质膜中的整合素结合来介导粘附，在质膜中它形成整合素和肌动蛋白细胞骨架之间的主要连接。细胞调节talin在质膜和细胞质之间的分配来控制细胞粘附。在这里，我们将核磁共振波谱 (NMR) 与亚细胞分级分离相结合，以表征两种不同的 THD-rod 结构域相互作用，这些相互作用控制着 talin 与肌动蛋白细胞骨架的相互作用或其在质膜上的定位。杆上离散的纽蛋白结合区域 (VBS1/2a; Tln1(482-787)) 和 THD 之间的相互作用会抑制踝蛋白与质膜的相互作用。此外，我们发现纽蛋白与 VBS1/2a 结合导致踝蛋白募集到质膜。因此，我们在结构上定义了 THD 和调节踝蛋白亚细胞定位的踝蛋白杆结构域之间的特定域间相互作用。
Talin, which is composed of head (THD) and rod domains, plays an important role in cell adhesion events in diverse species including most metazoans and Dictyostelium discoideum. Talin is abundant in the cytosol; however, it mediates adhesion by associating with integrins in the plasma membrane where it forms a primary link between integrins and the actin cytoskeleton. Cells modulate the partitioning of talin between the plasma membrane and the cytosol to control cell adhesion. Here, we combine nuclear magnetic resonance spectroscopy (NMR) with subcellular fractionation to characterize two distinct THD-rod domain interactions that control the interaction of talin with the actin cytoskeleton or its localization to the plasma membrane. Aninteraction between a discrete vinculin-binding region of the rod (VBS1/2a; Tln1(482-787)), and the THD restrains talin from interacting with the plasma membrane. Furthermore, we show that vinculin binding to VBS1/2a results in talin recruitment to the plasma membrane. Thus, we have structurally defined specific inter-domain interactions between THD and the talin rod domain that regulate the subcellular localization of talin.