Differential actin-dependent localization modulates the evolutionarily conserved activity of Shroom family proteins
Differential actin-dependent localization modulates the evolutionarily conserved activity of Shroom family proteins
复制标题
DOI：
10.1074/jbc.m512463200
复制
发表时间：
2006-07-21
影响因子：
4.8
通讯作者：
Hildebrand, Jeffrey D.
中科院分区：
文献类型：
--
作者：
Dietz, Megan L.;Bernaciak, Teresa M.;Hildebrand, Jeffrey D.
蘑菇是一种肌动蛋白相关的细胞形态决定因素，是小鼠和青蛙神经管闭合所必需的。蘑菇通过肌球蛋白II引起上皮细胞顶端收缩来调节这一过程。在这里，我们报告的蘑菇相关蛋白Apxl和KIAA 1202的特性及其在细胞结构中的作用。Shroom、Apxl和KIAA 1202表现出与肌动蛋白细胞骨架相互作用的不同能力。在成纤维细胞中，Shroom容易与肌动蛋白应力纤维结合并诱导成束，Apxl在皮质肌动蛋白上发现，KIAA 1202定位于F-肌动蛋白的细胞质群体。在上皮细胞中，Apxl和KIAA 1202不像Shroom那样诱导顶端收缩，但如果靶向顶端连接复合物，则具有这样做的能力。为了确定无脊椎动物中的蘑菇样蛋白的活性是否是保守的，我们测试了果蝇中唯一的蘑菇相关蛋白CG 8603激活收缩通路的能力。一种嵌合蛋白，由蘑菇靶向结构域和果蝇蛋白伸长收缩区组成。最后，我们表明，Apxl参与调节内皮细胞的细胞骨架组织和结构。我们预测蘑菇样蛋白调节细胞形态的能力在进化中是保守的，并且部分受亚细胞定位的调节。
Shroom is an actin-associated determinant of cell morphology that is required for neural tube closure in both mice and frogs. Shroom regulates this process by causing apical constriction of epithelial cells via a pathway involving myosin II. Here we report on characterization of the Shroom-related proteins Apxl and KIAA1202 and their role in cell architecture. Shroom, Apxl, and KIAA1202 exhibit differing abilities to interact with the actin cytoskeleton. In fibroblasts, Shroom readily associates with actin stress fibers and induces bundling, Apxl is found on cortical actin, and KIAA1202 is localized to a cytoplasmic population of F-actin. In epithelial cells, Apxl and KIAA1202 do not induce apical constriction as Shroom does, but have the capacity to do so if targeted to the apical junctional complex. To determine whether the activity of Shroom-like proteins is conserved in invertebrates, we have tested the ability of the lone Shroom-related protein in Drosophila, CG8603, to activate the constriction pathway. A chimeric protein consisting of the Shroom targeting domain and the Drosophila protein elicits constriction. Finally, we show that Apxl is involved in regulating the cytoskeletal organization and architecture of endothelial cells. We predict that the ability of Shroom-like proteins to regulate cellular morphology is conserved in evolution and is regulated in part by subcellular localization.